Green and controllable metal-free nitrification and nitration of arylboronic acids

Article abstract of DOI:10.1016/j.cclet.2012.03.028

A novel and green nitrating reagent has been developed for the nitrification and nitration of arylboronic acids, which can be controlled by the reaction conditions. The process provides an attractive alternative to the traditional nitration protocols.

Full text of DOI:10.1016/j.cclet.2012.03.028

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 643–646
www.elsevier.com/locate/cclet
Green and controllable metal-free nitrification and nitration
of arylboronic acids
*
Shuai Wang, Chun Chun Shu, Tao Wang, Jian Yu, Guo Bing Yan
Department of Chemistry, Lishui University, Lishui 32300, China
Received 28 December 2011
Available online 12 May 2012
Abstract
A novel and green nitrating reagent has been developed for the nitrification and nitration of arylboronic acids, which can be
controlled by the reaction conditions. The process provides an attractive alternative to the traditional nitration protocols.
# 2012 Guo Bing Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Nitrification; Nitration; Arylboronic acids
Aromatic nitro compounds are versatile building blocks in organic synthesis [1]. They have also found widespread
applications as pharmaceuticals, dyes, and materials [2]. Traditional methods for the synthesis of nitroaromatics are
via direct electrophilic aromatic substitution in the presence of mixtures of nitric and sulfuric acid, or dinitrogen
pentoxide. However, these methods suffer from issues of arrow functional group compatibility and poor
regioselectivity. Further, these nitrating agents are also good oxidants, which lead to oxidation of some substrates.
Therefore, the development of a new and safe nitro source in the nitration reaction with a broad substrate scope
remains an extremely attractive yet challenging task for organic chemists. In 2000, Prakash and co-workers firstly
reported the ipso-nitration of arylboronic acids with the combination of ammonium nitrate and trifluroacetic anhydride
as a nitro source [3]. The same group in 2004 made further modifications to the nitration protocol by using inorganic
nitrate salt and chlorotrimethylsilane, which acted as a selective and efficient nitrating agent [4]. An interesting
copper-catalyzed nitration of aryl iodides and bromides using n-Bu4NNO2 as a nitrating agent was discovered by
Saito’s group [5]. In 2009, Buchwald developed an efficient palladation-nitration protocol for the regioselective ipso-
nitration of aryl chlorides, triflates and nonaflates with more convenient and inexpensive NaNO2 as a nitrating agent
[6]. Very recently, inorganic nitrate or nitrite salts as nitrating agents have been reported on the basis of the metal-
catalyzed chelation-assisted C–H bond nitration [7]. Although significant advances were achieved in the transition
metal-catalyzed nitration of haloarenes or arenes for the synthesis of nitroarenes, critical issues remains regarding the
presence of metal impurities in the final product, which may restrict their practical application.
Therefore, alternative efficient metal-free process for nitration attracts attentions. In 2009, Savinov developed a
novel procedure for selective and efficient nitration of phenols using tert-butyl nitrite as a nitrating agent [8].
* Corresponding author.
E-mail address: gbyan@lsu.edu (G.B. Yan).
1001-8417/$ – see front matter # 2012 Guo Bing Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.03.028

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S. Wang et al. / Chinese Chemical Letters 23 (2012) 643–646
Table 1
Optimization of nitration of 4-tert-butylphenylboronic acid 1a with tert-butyl nitrite.a.
B(OH)2
NO2
+
NO
tBuONO
Solvent
1a
2a
2a'
c
Entry
Solvent
Oxidant
Temp. (8C)
Time (h)
Yield (%)b
2a/2a0
1
THF
Air
Air
Air
N2
rt
24
24
24
24
24
24
18
12
12
12
32
54
78
85
36d
82
80
82
83
85
28:72
24:76
22:78
7:93
2
CH2Cl2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
rt
3
rt
4
rt
5
H2O2
O2
rt
–
6
rt
30:70
89:11
>95:5
>95:5
>95:5
7
Air
Air
Air
Air
40
50
50
50
8
9e
10f
a
Unless otherwise noted, the reaction conditions are as follows: 4-tert-butylphenylboronic acid 1a (0.5 mmol), tBuONO (1.5 equiv.), in
anhydrous solvent (2 mL), under open air.
b
Isolated yield.
c
the ratios were determined by GC–MS.
d
Isolated yield of 2a.
tBuONO (2 equiv).
e
f
tBuONO (3 equiv).
Arylboronic acids have been widely used in organic synthesis for functional group transformations, due to commercial
availability and excellent stability to air and moisture [9]. Herein, we report a simple and controllable procedure for
nitrification and nitration of arylboronic acids using tert-butyl nitrite as a nitrating agent.
On the outset of this investigation, we used 4-tert-butylphenylboronic acid 1a as model substratewith tert-butyl nitrite
as a nitrating agent to screen suitable reaction conditions. Theresults were summarized in Table 1. When the reaction was
carried out in THF at the room temperature in air, the inspiring result was obtained that the ratio of 2a and 2a0 is 28–72
detected by GC–MS after 24 h (Table 1, entry 1). Encouraged by this initial result, we proceeded to optimize the reaction
conditions. The yields of the reaction significantly increased in CH2Cl2 and MeCN, but the ratio of 2a and 2a0 slightly
changed (Table 1, entries 2 and 3). As is well known, nitroso compounds can be easily transfered into nitro compounds
underoxidant conditions. Thus, wewanted toobtain single nitrationproduct 2aornitrification product 2a0 via controlling
the reaction conditions. To our delight, when the reaction was carried out under N2 at the room temperature in MeCN,
nitrification product 2a0 was exclusively obtained with 85% yield (Table 1, entry 4). On the other hand, when H2O2 was
used as oxidant, the mixture products were detected by GC-Mass, including 4-tert-butylphenol, 4-tert-butyl-2-
nitrophenol and 2a (Table 1, entry 5). The reaction was carried out under O2 balloon, affording the mixture products 2a
and 2a0 with 82% yield (Table 1, entry 6). Interestingly, the nitration product 2a was exclusively obtained with excellent
yields by increasing the reaction temperature (Table 1, entries 7 and 8). In addition, theyields of thereaction were slightly
improved by increasing the amount of tert-butyl nitrite (Table 1, entries 9 and 10).
Because nitroso compounds are poisonous and rarely used in organic synthesis, we only investigated the nitration
reactions of a series of arylboronic acids. The results were summarized in Table 2. It was observed that the reaction was
marginally affected by electronic effects of the substituents of arylboronic acids. The reaction with electron-donating
substituted arylboronic acids proceeded smoothly and afforded the corresponding nitro compounds in good yields
(Table 2, entries 1–10). Moreover, it was found that the yields were obviously affected by the steric hindrance of
arylboronic acids. The yields of para-electron-donating substituted arylboronic acids were higher than that of ortho-,
meta-substituted arylboronic acids (Table 2, entries 2–4). However, the substituted arylboronic acids bearing electron-
deficient groups showed lower reactivity (Table 2, entries 11–13). For examples, 1-chloro- and 1-trifluoromethyl-4-
nitrobenzenes were obtained with 52% and 26% yields from 4-chloro- and 4-trifluoro- methylphenylboronic acid,

S. Wang et al. / Chinese Chemical Letters 23 (2012) 643–646
645
Table 2
Nitration of arylboronic acid 1 with tert-butyl nitrite.a
Entry
1
Arylboronic acids (1)
Nitroaromatics (2)
Yield (%)b
82
1a
B(OH)2
2a
NO2
2
3
78
68
1b
2b
NO2
B(OH)2
1c
1d
B(OH)2
B(OH)2
B(OH)2
2c
2d
2e
NO2
NO2
NO2
4
5
51
68
1e
6
7
81
73
1f
2f
NO2
MeO
MeO
B(OH)2
MeO
MeO
1g
2g
B(OH)2
NO2
8
9
68
74
1h
2h
B(OH)2
NO2
1i
2i
2j
B(OH)2
NO2
NO2
10
B(OH)2
72
1j
11
12
13
52
26
1k
Cl
B(OH)2
2k
Cl
NO2
1l
2l
NO2
F3C
NC
B(OH)2
F3C
NC
Trace
1m
2m
NO2
B(OH)2
a
Unless otherwise noted, the reaction conditions are as follows: Aryllboronic acid 1a-m (0.5 mmol), tBuONO (1.5 equiv), in anhydrous MeCN
(2 mL), under open air, at 50 8C.
Isolated yield.
b
respectively (Table 2, entries 11 and 12). For the nitration of 3-cyano phenylboronic acid, only small amount of the
desired product was detected by GC–MS (Table 2, entry 13).
Although the detailed mechanism for this process awaits further investigation, a plausible mechanism for the
nitration of arylboronic acid is proposed (Scheme 1). It is likely that there exists a prominent electronic interaction
between the boronic acid group and tert-butyl nitrite through boron and the oxygen atom due to the high oxophilicity
of boron. Next, the migration of phenyl group from tetracoordinated ate complexItakes place, and then the N–O bond
cleavge affords 1-nitrosobenzene, which is easily transfered into nitrobenzene under oxidant conditions.

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S. Wang et al. / Chinese Chemical Letters 23 (2012) 643–646
HO OH
HO
OH
NO
NO2
B
B
O
O
[O]
NO
NO
Scheme 1. Mechanistic rationale.
In summary, we have developed a green method for the nitrification and nitration of arylboronic acids. This
environmentally friendly and simple experimental procedure will attract much attention in academic and industrial
fields. Further investigation of the detailed mechanism and the scope of substrates is currently underway in our lab.
Acknowledgments
We are grateful for the financial support by New-Shoot Talented Man Plan Project of Zhejiang Province (No.
2011R429012).
References
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