Nitration of aromatic compounds under neutral conditions using the Ph 2PCl/I2/AgNO3 reagent system

Article abstract of DOI:10.1016/j.tetlet.2011.07.097

Aromatic compounds were nitrated efficiently under essentially neutral conditions by employing Ph₂PCl in the presence of I₂ and AgNO₃. This method minimizes waste products compared to traditional methods and gives the corresponding mononitro derivatives in good to excellent yields in dichloromethane at room temperature.

Full text of DOI:10.1016/j.tetlet.2011.07.097

Tetrahedron Letters 52 (2011) 5081–5082
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Tetrahedron Letters
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Nitration of aromatic compounds under neutral conditions
using the Ph2PCl/I2/AgNO3 reagent system
⇑
Najmeh Nowrouzi , Mohammad Zareh Jonaghani
Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Aromatic compounds were nitrated efficiently under essentially neutral conditions by employing Ph2PCl
in the presence of I2 and AgNO3. This method minimizes waste products compared to traditional methods
and gives the corresponding mononitro derivatives in good to excellent yields in dichloromethane at
room temperature.
Received 2 May 2011
Revised 6 July 2011
Accepted 22 July 2011
Available online 27 July 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Chlorodiphenylphosphine
Iodine
Nitration
Aromatic compounds
Nitration is one of the oldest and most extensively studied reac-
tions. Moreover, this process has been favored for the manufacture
of explosives, dyes, plastics, and industrial solvents.1 Aromatic nitra-
tion is important, because it is a convenient way of adding an amino
group to the ring. The classical nitration is commonly performed in
strongly acidic polar medium such as nitric acid and concentrated
sulfuric acid.1,2 Such conditions lead to excessive acid waste which
is environmentally unfriendly, expensive to treat, and contribute
to heavy corrosion of equipment. The problems associated with
mixed acids have prompted the search for alternative methods,
and various nitrating agents have been studied under different
conditions.3 Among these, most suffer from drawbacks, such as
regioselectivity, over-nitration, and competitive oxidation of
substrates,4 or are still carried out under acidic conditions.3f,5 Hence,
there is still a need for the development of new methods for the
nitration of aromatic compounds. Herein, we report a mild, easy to
operate, and efficient protocol for the nitration of aromatic
compounds.
Our procedure employs chlorodiphenylphosphine (CDP) in con-
junction with molecular iodine to perform a very clean and efficient
nitration under neutral conditions. The resulting phosphorus by-
product, diphenylphosphinic acid, can be removed with an aqueous
basic solution during work-up.
In order to ascertain the optimum conditions, several reactions
were carried out on anisole as a model substrate by varying the
amount of reagents and solvent.
The best result was obtained with 1.1 equiv of both Ph2PCl and
I2, and 2.2 equiv of AgNO3 for nitration of 2.0 equiv of anisole in
CH2Cl2 at room temperature (Scheme 1).
Having established the optimum reaction conditions, various
aromatic compounds were subjected to nitration and the results
are summarized in Table 1.
Aromatic compounds having activating groups (entries 1–5)
readily underwent nitration in excellent yields. Deactivated
aromatic compounds were not converted into nitrobenzene deriv-
atives with this reagent system (entries 9–11). It is interesting to
note that among halobenzenes, only iodobenzene reacted under
our conditions and produced the corresponding products in mod-
erate yields; chloro- and bromobenzene failed to nitrate even after
prolonged reaction times at reflux. Polyaromatic hydrocarbons
such as naphthalene (entry 6) and anthracene (entry 7) underwent
smooth nitration under the same experimental conditions. It is
pertinent to mention that nitropolyaromatic hydrocarbons are
important as intermediates for the synthesis of anti-tumor agents.6
Nitration of phenol has been studied using various nitrating agents
OCH3
OCH3
OCH3
NO2
Ph2PCl (1.1 eq), I2 (1.1 eq)
+
AgNO3 (2.2 eq)
CH2Cl2, r.t.
NO2
2.0 eq
⇑
Corresponding author. Tel.: +98 771 4222341; fax: +98 771 4541494.
E-mail address: nowrouzi@pgu.ac.ir (N. Nowrouzi).
Scheme 1.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.097

5082
N. Nowrouzi, M. Zareh Jonaghani / Tetrahedron Letters 52 (2011) 5081–5082
Table 1
aromatic compounds along with diphenylphosphinic acid as
shown in Scheme 2.
Nitration of aromatic compounds using Ph2PCl/I2/AgNO3 in CH2Cl2 at room
temperature
Inthisreaction, thesilversaltis recoveredbyfiltrationofthereac-
tion mixture. In a typical experiment: to a flask containing a stirred
mixture of Ph2PCl (1.1 mmol, 0.202 mL) and I2 (1.1 mmol, 0.279 g) in
CH2Cl2 (5 mL), was added silver nitrate (2.2 mmol, 0.373 g) at room
temperature. N,N-Dimethylaniline (2.0 mmol, 0.252 mL) was then
added to the reaction mixture. After 10 min, the mixture was filtered
to remove precipitated AgCl and AgI. The residue was washed with
saturated aqueous Na2CO3 (3 Â 5 mL) until all the diphenylphosphi-
nic acid was removed from the organic phase. The aqueous phase
was separated and the organic phase washed with aqueous Na2S2O3
(2 Â 5 mL) to remove the excess I2 and then H2O (5 mL), dried, and
concentrated. Column chromatography of the residue was per-
formed on silica gel using n-hexane/EtOAc (4:1) as eluent to give
pure 2-nitro- and 4-nitro-N,N-dimethylanilines in 15% and 77%
yields, respectively. 4-Nitro-N,N-dimethylaniline: IR (KBr) 800,
Entry
1
Aromatic compound
Anisole
Time
Yielda (%)
35 min
ortho: 19
para: 70
2-Nitro: 75
ortho: 20
para: 66
3-Nitro: 92
ortho: 15
para: 77
1-Nitro: 80
9-Nitro: 88
ortho: 10
para: 57
—
2
3
4-Iodoanisole
Toluene
4 h
1 h
4
5
Indole
N,N-Dimethylaniline
20 min
10 min
6
7
8
Naphthalene
Anthracene
Iodobenzene
4 h
3.5 h
24 h
9
10
11
12
Chlorobenzene
Bromobenzene
Cyanobenzene
Phenol
24 h
24 h
24 h
20 min
—
—
ortho: 35
para: 56
2-Nitro: 80
4-Nitro: 72
2-Nitro: 80
2-Nitro: 94
2-Nitro: 95
2-Nitro: 90
1300, 1350, 1500, 1525, 1600, 2900–3000 cmÀ1
;
1H NMR
(250 MHz, CDCl3): d (ppm) 2.89 (6H, s), 6.32 (2H, d, J = 8.4), 7.8
(2H, d, J = 8.4); 13C NMR (62.9 MHz, CDCl3): d (ppm) 30.2, 110.5,
126.4, 138.0, 154.4.
13
14
15
16
17
18
4-Nitrophenol
2-Nitrophenol
4-Bromophenol
p-Cresol
4-Ethylphenol
4-Methoxyphenol
5.5 h
6 h
5 h
5 min
5 min
5 min
In conclusion, we have demonstrated the ability of the reagent
system, Ph2PCl/I2/AgNO3 to perform nitration of aromatic com-
pounds under essentially neutral conditions. Application of this re-
agent system allows for nitration of acid-sensitive substrates
compared to traditional methods. In addition, experimental sim-
plicity, readily available reagents, easy handling, and absence of
di-nitrated and poly-nitrated products are other advantages of
our system.
a
Isolated yield.
I
I
2 AgNO3
Ph2PCl
I2
Ph2P
+
Cl
- AgCl
- AgI
I
Acknowledgment
Ph
I
2 ArNO2
+
Ph2P(O)OH
We thank the Persian Gulf University Research Council for gen-
erous partial financial support of this study.
P
O2N
O
O NO2
Ph
ArH
Scheme 2.
ArH
II
References and notes
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VCH: New York, 1989; (b) Schofield, K. Aromatic Nitration; University Press:
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185, 305.
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similar conditions to those described above gave the corresponding
nitro derivatives in excellent yields. Phenols with electron-
donating or electron-withdrawing groups also reacted smoothly
under mild conditions to afford the expected products in good to
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However, lower yields and longer reaction times were observed
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phenyl moiety. For example, quantitative nitration of p-cresol
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ring decreased slightly the yield and increased the reaction time.
A possible mechanism for this reaction is shown in Scheme 2.
Treatment of Ph2PCl with I2 forms intermediate I. Addition of
AgNO3 produces the intermediate II which is accompanied by the
precipitation of AgCl and AgI. This reactive intermediate then
reacts with the aromatic ring to produce the corresponding nitro
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