Silver(I)-Promoted ipso-Nitration of Carboxylic Acids by Nitronium Tetrafluoroborate

Article abstract of DOI:10.1021/acs.joc.5b02133

A novel and efficient method for the regioselective nitration of a series of aliphatic and aromatic carboxylic acids to their corresponding nitro compounds using nitronium tetrafluoroborate and silver carbonate in dimethylacetamide has been described. This transformation is believed to proceed via the alkyl-silver or aryl-silver intermediate, which subsequently reacts with the nitronium ion to form nitro substances. Mild reaction conditions, tolerant of a broad range of functional groups, and formation of only the ipso-nitrated products are the key features of this methodology when compared to known methods for syntheses of nitroalkyls and nitroarenes.

Full text of DOI:10.1021/acs.joc.5b02133

Article
pubs.acs.org/joc
Silver(I)-Promoted ipso-Nitration of Carboxylic Acids by Nitronium
Tetrafluoroborate
Palani Natarajan,* Renu Chaudhary, and Paloth Venugopalan
Department of Chemistry & Centre for Advanced Studies in Chemistry, Panjab University, Chandigarh 160 014, India
S
* Supporting Information
ABSTRACT: A novel and efficient method for the regioselective
nitration of a series of aliphatic and aromatic carboxylic acids to their
corresponding nitro compounds using nitronium tetrafluoroborate
and silver carbonate in dimethylacetamide has been described. This
transformation is believed to proceed via the alkyl-silver or aryl-silver
intermediate, which subsequently reacts with the nitronium ion to
form nitro substances. Mild reaction conditions, tolerant of a broad
range of functional groups, and formation of only the ipso-nitrated
products are the key features of this methodology when compared to
known methods for syntheses of nitroalkyls and nitroarenes.
efficient and practical for the synthesis of potentially useful
nitro compounds.
INTRODUCTION
■
The ipso-nitration reaction,1 employed for the synthesis of a
wide variety of nitro compounds, is a practical alternative to the
classical electrophilic nitration reaction that encounters several
problems including polynitration and competitive oxidation of
substrates. Although several leaving groups such as alkyls,2
acyls,3 boronic acids,4 esters,3 halogens,3c,5 sulfonic acids,6 and
carboxylic acids7 were found to be displaced by a nitro group,
only ipso-nitration of arylboronic acids has been studied
intricately and consistently.4 Undoubtedly, reported methods
of deborylative nitration of arylboronic acids are useful;
however, the principal drawbacks associated with these
protocols are use of highly toxic and explosive reagents such
as bismuth nitrate,4a cadmium nitrate,4b mixture of sodium
nitrate and palladium,4c etc.1 Moreover, many boronic acids8
are unstable (readily lose water/boron at ambient conditions)
and expensive.9 As a consequence, the elaborate and systematic
study of replacement of other substituent/s (i.e., alkyls/acyls/
carboxylic esters/halogens/sulfonic acids/carboxylic acids) by a
nitro group is very desirable and remains a challenging area for
exploration.
It is well-known that carboxylic acids undergo decarbox-
ylation most efficiently in the presence of silver salts (relative to
copper salts) to generate a carbon nucleophile in situ.13 This
proficiency is likely due to their (silver salts) lower electro-
negativity and greater expansion of d-orbitals, which promote
the decarboxylation of substrates.13a Of course, various silver
salts have been employed as catalysts for the decarboxylative
carbon−carbon, carbon−silicon, carbon−oxygen, carbon−
boron, carbon−sulfur, carbon−phosphorus, and carbon−
halogen bond-forming reactions.11,13,14 Inspired by these
reports and our previous works on the decarboxylative
oxidation of polycyclic aromatic compounds,15 herein we
describe a novel and efficient approach for the ipso-nitration
of a broad range of carboxylic acids with nitronium
tetrafluoroborate (NO2BF4) as a nitrating agent and silver
carbonate (Ag2CO3) as a decarboxylation reagent in
dimethylacetamide (DMA), cf., Scheme 1. To the best of our
knowledge, no attempt to perform the ipso-nitration of
carboxylic acids using a mixture of NO2BF4 and Ag2CO3 has
been reported in the literature.
Carboxylic acids10 have long served as precursors for a wide
array of organic transformations, because they are inexpensive,9
easy to handle, chemically nontoxic, straightforward to
synthesize, air and moisture insensitive, and readily available
in great structural forms.10c In addition, huge numbers of
homo- and cross-coupling reactions making use of carboxyl
substituents as leaving groups for regioselective couplings have
been reported.11 Circumstantially only a single report on the
ipso-nitration of aromatic carboxylic acids, using cellulose
supported copper nanoparticles and bismuth(III) nitrate, has
been described so far.12 Further investigations would thus be
crucial to make the decarboxylative nitration reaction more
RESULTS AND DISCUSSION
■
In order to optimize the reaction condition, benzoic acid (1C)
was chosen as a model substrate, and NO2BF4 and Ag2CO3,
respectively, were used as nitrating as well as decarboxylation
agents. The results of optimization reactions performed under a
variety of conditions are summarized in Table 1. Investigations
of the model reaction in various anhydrous solvents including
Received: June 30, 2015
© XXXX American Chemical Society
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DOI: 10.1021/acs.joc.5b02133
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13) provided no product indicating the importance of a silver
ion that helps stabilize the resulting anion upon loss of carbon
dioxide. Similar behaviors have been reported for several
silver(I) catalyzed decarboxylative cross-coupling reactions.13,14
Further optimization of the amount of NO2BF4 showed that a
slight excess (0.5 mmol) is necessary to achieve high yields
(Table 1 and entry 14) of 1N in short duration. It is
noteworthy that NO2BF4 was effective only in the presence of
Ag2CO3 (Table 1 and entry 18). Likewise, in the absence of
NO2BF4 but with 1.0/2.0 mmol of Ag2CO3 (Table 1 and
entries 19 and 20) no nitration was detected. Clearly, both
NO2BF4 and Ag2CO3 are essential for the reaction. Finally,
raising the temperature from 80 to 120 °C with 10 °C
increments/experiment led to 1N in more than 90% yield in
significantly short duration, cf., Table 1 and entries 21−23. No
product formation was noticed when the reaction was carried
out at room temperature (Table 1 and entry 24). Thus, the
optimized conditions for the ipso-nitration of carboxylic acids
can be defined as follows: 1.0 mmol of substrate, 1.5 mmol of
Scheme 1. NO2BF4 and Ag2CO3 Mediated Decarboxylative
Nitration of Carboxylic Acids to Their Corresponding Nitro
Compounds Reported in This Work
acetonitrile, chloroform, dichloromethane, dichloroethane,
DMA, tetrahydrofuran, and tetrachloroethane suggested that
anhydrous DMA was the best medium for the ipso-nitration of
1C (Table 1 and entry 5). This likely reason is that a relatively
polar solvent is necessary to dissolve Ag2CO3 and NO2BF4,
since they have limited solubility in medium polar solvents.
There was next an attempt to arrive at an optimum
stoichiometry of Ag2CO3 and NO2BF4 to 1C (1.0 mmol) for
1N synthesis in DMA. As shown in Table 1 (entries 5, 9, 10,
and 11), higher amounts of Ag2CO3 neither increased the
product yield nor lowered the reaction time drastically. The
best result (Table 1 and entry 8) was obtained by carrying out
the reaction with 0.5 mmol of Ag2CO3 to 1.0 mmol of 1C.
Under this stoichiometric condition, alternative bases such as
K2CO3 (Table 1 and entry 12) and Na2CO3 (Table 1 and entry
NO2BF4, 0.5 mmol of Ag2CO3, anhydrous DMA, and 90
5
°C. Under this optimized condition, formation of 1N from 1C
1
was confirmed by the H NMR titration experiments as well,
cf., Figure 1. The easily recognizable ortho protons (of 1C) at δ
a
Table 1. Optimization of Reaction Conditions for Silver Carbonate-Promoted ipso-Nitration of Carboxylic Acids
b
b
c
d
entry
Ag2CO3 (mmol)
NO2BF4 (mmol)
T (°C)
solvent
time (h)
yield (%)
1
2
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
1.5
2.0
3.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.5
2.0
2.5
3.0
2.0
0
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
90
100
110
20
80
90
110
acetonitrile
chloroform
36
36
36
36
18
36
36
18
18
16
16
36
36
15
14
12
12
36
36
36
13
12
12
48
18
13
12
< 5
< 5
NR
NR
88
3
dichloromethane
dichloroethane
DMA
4
5
6
tetrahydrofuran
tetrachloroethane
DMA
<5
NR
87
7
8
9
DMA
89
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
DMA
87
DMA
88
e
0.5
DMA
NR
NR
93
f
0.5
DMA
0.5
0.5
0.5
0.5
0
DMA
DMA
92
DMA
93
DMA
94
g
DMA
NR
h
1.0
2.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
DMA
NR
h
0
DMA
NR
1.5
1.5
1.5
1.5
1.0
1.5
1.5
DMA
92
DMA
91
DMA
89
DMA
NR
i
DMA
79
i
DMA
84
i
DMA
81
a
Unless otherwise stated, all reactions were carried out with 1.0 mmol of 1C and the indicated amounts of Ag2CO3 and NO2BF4 under nitrogen gas
b
c
d
atmosphere. Ag2CO3 and NO2BF4 were dried under vacuum before use. Double distilled solvents were employed. Yield of 1N was determined by
e
f
g
GC analysis using an internal standard. K2CO3 used instead of Ag2CO3. Na2CO3 used instead of Ag2CO3. Obtained 3-nitrobenzoic acid (<10%).
h
i
Detected decarboxylated compound. Reaction performed under open air atmosphere. DMA: dimethylacetamide. NR: no reaction.
B
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Figure 1. 1H NMR spectroscopic monitoring (0−12 h) of conversion of 1C into 1N in DMA-d3 solution. Notice that a new peak (*) at 8.19 ppm
⧫
gradually appeared, while a signal ( ) at 8.12 ppm has disappeared indicating the product (1N) formation.
= 8.12 ppm completely disappeared within 12 h, while a new
peak at δ = 8.19 ppm corresponding to 1N originated.
1 and entries 19−20), and the reactions did not succeed,
indicating both NO2BF4 and Ag2CO3 played an important role
in the product formation. Ag(I) salts have been shown to
mediate the decarboxylation of carboxylic acids in solu-
tions.13,14 Accordingly, the proposed mechanism (Figure 2)
starts with an anion exchange at the silver center to give the
metal carboxylate, which in turn provides an arylmetal species
by extrusion of carbon dioxide. A subsequent reaction with
nitronium ion results in the desired nitro compound forming,
leaving the silver tetrafluoroborate as a byproduct. It is
noteworthy to mention that, in the absence of NO2BF4, only
the decarboxylated compound was detected indicating the
formation of aryl-silver species as an intermediate.
Encouraged by the remarkable results obtained with the
above reaction conditions (Table 1), and to show the generality
of this new protocol, it was applied to a series of electronically
diversified aliphatic and aromatic carboxylic acids (Table 2).
We were delighted to find that our protocol tolerates a wide
range of functionalities. Indeed, aryl-/heteroaryl-/polyaryl
carboxylic acids with electron donating (CH3, OCH3, C6H5)
and withdrawing (F, Cl, Br, CN, CF3, CHO, COOCH3) groups
afforded moderate to good yields of corresponding nitroarenes
(Table 2). Similarly, no significant effect was observed for
sterically demanding substrates that gave good yields of
expected nitro compounds (Table 2 and entries 3, 10, 12, 16,
20−28). This method, moreover, is applicable to the
nitrodecarboxylation of aliphatic carboxylic acids (Table 2
and entries 22−28) too. Therefore, the present methodology
proved of general applicability for the ipso-nitration of
carboxylic acids to nitro derivatives.
To demonstrate the applicability of this method, we aimed to
prepare two nitro drugs, namely, fexinidazole (30N)43 and
nitazoxanide (31N)44 (Scheme 2), from their carboxylic acid
precursors under standard conditions described in Table 1. In
both cases, the reactions were complete within 12 h affording
the desired products in 71−82% yield. Thus, the ipso-nitration
reaction described here offers a domain for synthesis of highly
functionalized nitro compounds (Table 2) including nitro drugs
(Scheme 2) that cannot be achieved by traditional electrophilic
nitration reaction1 known to overoxidize the substrate.
CONCLUSIONS
■
In summary, we have introduced the mixture of nitronium
tetrafluoroborate and silver carbonate as an efficient and novel
reagent system for the synthesis of a variety of nitro
compounds including fexinidazole (30N) and nitazoxanide
(31N) from their carboxylic acid precursors. The principal
advantages of this method include regioselectivity, use of
relatively inexpensive carboxylic acids as precursors, broad
tolerance of functional groups, moderate to good yields of
targeted products, as well as avoidance of the use of strong
acids. We believe that the ipso-nitration reaction reported here
may be a valuable methodology for the synthesis of a wide
range of functional materials46 including drugs, dyes, explosives,
pharmaceuticals, and plastics derived from nitro feedstocks.
The plausible reaction mechanism for the ipso-nitration of
carboxylic acids is outlined in Figure 2 on the basis of blank
experiments (Table 1 and entries 18−20 and 25−27) and
earlier reports.45 To understand the roles of NO2BF4 and
Ag2CO3, we carried out blank experiments with 1C and
NO2BF4 (in the absence of Ag2CO3, Table 1 and entry 18) as
well as with 1C and Ag2CO3 (in the absence of NO2BF4, Table
EXPERIMENTAL SECTION
■
General Aspects. Solvents were double distilled prior to use. All
commercial chemicals were used as received. All reactions were carried
out under nitrogen gas atmosphere using standard Schlenk techniques.
Reactions were monitored by analytical thin layer chromatography on
silica gel with visualization under UV light. Column chromatography
was carried out on silica gel using 60−120 mesh powder. NMR spectra
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a
Table 2. Substrate Scope for the Decarboxylative Nitration of Alkyl and Aryl Carboxylic Acids to Nitro Compounds
a
Unless stated otherwise, all reactions were performed with carboxylic acid (1.0 mmol), NO2BF4 (1.5 mmol), and Ag2CO3 (0.5 mmol) in DMA at
b
90 5 °C under nitrogen gas atmosphere. Isolated yield. The products were characterized by their comparison with known compounds.
were recorded using a 300 MHz spectrometer in deuterated solvents.
Melting points were obtained at a heating rate of 2°/min and are
uncorrected.
General Procedure for the ipso-Nitration of Carboxylic
Acids. To a suspension of carboxylic acid (1.0 mmol) and Ag2CO3
(0.5 mmol) in 10 mL of DMA was added NO2BF4 (1.5 mmol). The
resultant mixture was stirred at 90 5 °C for 12 h. Subsequently, the
reaction mixture was cooled down to room temperature, diluted with
20 mL of water, and extracted with ethyl acetate (3 × 20 mL). The
combined organic layers were washed with brine (2 × 15 mL), dried
over anhydrous Na2SO4, and evaporated in a rotary evaporator under
reduced pressure. The crude product was purified by either column
chromatography on silica gel using 5−20% ethyl acetate in hexane or
recrystallization employing ethyl acetate−hexane mixture to afford the
desired product. The purity of the compound was confirmed by
1
melting point and H and 13C NMR measurements, vide infra.
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Scheme 2. Synthesis of Fexinidazole (30N, Top) and Nitazoxanide (31N, Bottom) from their Carboxylic Acid Precursors
Methyl-4-nitrobenzoate (9N).23 Light-yellow solid (158 mg, 87%),
mp 90−91 °C (lit. 91−92 °C).23 Rf 0.54 in ethyl acetate−hexane
1
(0.5:9.5). H NMR (CDCl3) δ (ppm): 3.99 (s, 3H), 8.24 (d, J = 9.6
Hz, 2H), 8.28 (d, J = 9.6 Hz, 2H). 13C NMR (CDCl3) δ (ppm): 52.8,
123.4, 130.7, 135.5, 150.6, 165.0.
3-Chloronitrobenzene (10N).24 Light-yellow solid (126 mg, 80%),
mp 45−46 °C (lit. 46−47 °C).24 Rf 0.79 in ethyl acetate−hexane
1
(0.5:9.5). H NMR (CDCl3) δ (ppm): 7.49−7.53 (m, 1H), 7.68 (d, J
= 8.4 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.22 (s, 1H). 13C NMR
(CDCl3) δ (ppm): 121.7, 123.8, 130.5, 134.7, 135.5, 148.9.
2-Nitrobenzaldehyde (11N).25 Light-yellow solid (118 mg, 78%),
mp 43 °C (lit. 42−44 °C).25 Rf 0.57 in ethyl acetate−hexane (0.5:9.5).
1H NMR (CDCl3) δ (ppm): 7.76−7.84 (m, 3H), 8.05−8.13 (m, 1H),
10.43 (s, 1H). 13C NMR (CDCl3) δ (ppm): 124.5, 129.7, 131.4, 133.8,
Figure 2. Proposed reaction mechanism for the decarboxylative
nitration reaction.
134.3, 149.6, 188.2.
7-Nitro-1-tetralone (12N).26 Yellow solid (166 mg, 87%), mp 104−
105 °C (lit. 103−104 °C).26 Rf 0.55 in ethyl acetate−hexane (0.5:9.5).
1H NMR (CDCl3) δ (ppm): 2.04−2.09 (m, 2H), 2.72−2.80 (m, 4H),
7.63 (d, J = 8.8 Hz, 1H), 8.42 (d, J = 8.8 Hz, 1H), 8.49 (s, 1H). 13C
NMR (CDCl3) δ (ppm): 22.2, 29.7, 38.6, 122.5, 127.0, 130.2, 133.3,
147.2, 150.9, 195.9.
Nitrobenzene (1N). Pale yellow oil (115 mg, 93%). Rf 0.81 in ethyl
1
acetate−hexane (0.5:9.5). H NMR (CDCl3) δ (ppm): 7.52 (m, 2H),
7.64 (m, 1H), 8.19 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3) δ (ppm):
123.4, 129.4, 134.7, 148.1.
5-Nitro-2-furaldehyde (2N).16 Yellow solid (123 mg, 87%), mp 35
2-Nitrobiphenyl (13N).27 Light-yellow solid (175 mg, 88%), mp
35−36 °C (lit. 36−37 °C).27 Rf 0.72 in ethyl acetate−hexane (0.5:9.5).
1H NMR (CDCl3) δ (ppm): 7.34−7.39 (m, 2H), 7.42−7.48 (m, 3H),
7.54 (dd, J = 7.6, 1.2 Hz, 1H), 7.59−7.78 (m, 2H), 7.91 (dd, J = 7.6,
1.2 Hz, 1H). 13C NMR (CDCl3) δ (ppm): 125.8, 129.7, 130.1, 130.6,
133.7, 134.5, 137.6, 139.5, 151.4.
°C (lit. 35−36 °C).16 Rf 0.67 in ethyl acetate−hexane (0.5:9.5). H
1
NMR (CDCl3) δ (ppm): 7.82 (d, J = 8.2 Hz, 1H), 7.85 (d, J = 8.2 Hz,
1H), 9.97 (s, 1H). 13C NMR (CDCl3) δ (ppm): 111.8, 119.3, 151.2,
178.9.
4-Nitrotoluene (3N).17 Light-yellow solid (117 mg, 85%), mp 52−
53 °C (lit. 52 °C).17 Rf 0.80 in ethyl acetate−hexane (0.5:9.5). H
1
4-Nitrodibenzo[b,d]furan (14N).28 Yellow solid (179 g, 84%), mp
137−138 °C (lit. 137−138 °C).28 Rf 0.67 in ethyl acetate−hexane
(1:9). 1H NMR (CDCl3) δ (ppm): 7.46−7.51 (m, 2H), 7.57 (t, J = 7.4
Hz, 1H), 7.68−7.79 (m, 2H), 7.99 (d, J = 7.2 Hz, 1H), 8.26 (d, J = 7.2
Hz, 1H). 13C NMR (CDCl3) δ (ppm): 112.4, 120.8, 122.2, 122.7,
122.9, 124.0, 126.9, 128.3, 128.9, 134.0, 148.5, 156.8.
NMR (CDCl3) δ (ppm): 2.46 (s, 3H), 7.33 (d, J = 8.4 Hz, 2H), 8.01
(d, J = 8.4 Hz, 2H). 13C NMR (CDCl3) δ (ppm): 21.5, 123.5, 129.8,
146.1, 146.5.
3-Methyl-4-nitroanisole (4N).18 Light-yellow solid (130 mg, 79%),
mp 54−55 °C (lit. 54−55 °C).18 Rf 0.72 in ethyl acetate−hexane
(0.5:9.5). 1H NMR (CDCl3) δ (ppm): 2.62 (s, 3H), 3.86 (s, 3H), 6.79
(s, 1H), 6.83 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H). 13C NMR
(CDCl3) δ (ppm): 21.6, 55.8, 111.9, 117.5, 127.5, 137.0, 142.2, 163.2.
2-Fluoro-4-nitroanisole (5N).19 Tan solid (134 mg, 78%), mp 96−
97 °C (lit. 95−96 °C).19 Rf 0.71 in ethyl acetate−hexane (0.5:9.5). 1H
NMR (CDCl3) δ (ppm): 4.01 (s, 3H), 7.05 (d, J = 8.8 Hz, 1H), 7.98
(s, 1H), 8.06 (d, J = 8.8 Hz, 1H). 13C NMR (CDCl3) δ (ppm): 56.9,
112.4 (d, J = 24 Hz), 120.9, 140.8 (d, J = 6.7 Hz), 149.4, 152.3 (d, J =
215 Hz), 153.6.
4-Nitro-9-fluorenone (15N).29 Lemon-yellow solid (187 mg, 83%),
mp 174−175 °C (lit. 174−176 °C).29 Rf 0.57 in ethyl acetate−hexane
1
(1:9). H NMR (CDCl3) δ (ppm): 7.44−7.48 (m, 2H), 7.63 (d, J =
7.6 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 7.4 Hz, 1H), 8.03
(m, 2H). 13C NMR (CDCl3) δ (ppm): 124.9, 125.9, 128.6, 129.9,
130.3, 134.4, 135.7, 136.5, 137.2, 140.5, 145.0, 191.2.
2-Nitroanthraquinone (16N).30 Yellow solid (218 mg, 86%), mp
186 °C (lit. 185−186 °C).30 Rf 0.47 in ethyl acetate−hexane (2:8). 1H
NMR (CDCl3) δ (ppm): 7.86−7.92 (m, 2H), 8.35−8.47 (m, 2H),
8.52 (d, J = 8.4 Hz, 1H), 8.61 (m, 1H), 9.14 (d, J = 8.4 Hz, 1H). 13C
NMR (CDCl3) δ (ppm): 121.2, 126.27, 126.31, 126.6, 127.8, 131.7,
131.8, 133.2, 133.6, 135.5, 149.8, 179.6, 180.1.
4-Bromonitrobenzene (6N).20 Yellow solid (170 mg, 84%), mp
124−125 °C (lit. 123−124 °C).20 Rf 0.82 in ethyl acetate−hexane
1
(0.5:9.5). H NMR (CDCl3) δ (ppm): 7.69 (d, J = 8.4 Hz, 2H), 8.11
(d, J = 8.4 Hz, 2H). 13C NMR (CDCl3) δ (ppm): 125.0, 129.9, 132.7,
147.1.
3-Nitro-2,6-lutidine (17N).31 Brownish yellow solid (113 mg, 74%),
mp 37 °C (lit. 38 °C).31 Rf 0.32 in ethyl acetate−hexane (2:8). H
1
4-Nitrobenzonitrile (7N).21 Light-yellow solid (120 mg, 81%), mp
141−142 °C (lit. 140−142 °C).21 Rf 0.56 in ethyl acetate−hexane
NMR (CDCl3) δ (ppm): 2.61 (s, 3H), 2.86 (s, 3H), 7.16 (d, J = 8.4
Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H). 13C NMR (CDCl3) δ (ppm): 24.5,
24.9, 121.8, 133.5, 143.9, 154.1, 163.8.
1
(0.5:9.5). H NMR (CDCl3) δ (ppm): 7.88 (d, J = 8.4 Hz, 2H), 8.33
(d, J = 8.4 Hz, 2H). 13C NMR (CDCl3) δ (ppm): 116.8, 118.2, 124.3,
133.5, 149.9.
5-Nitroisoquinoline (18N).32 Yellow solid (138 mg, 79%), mp
108−109 °C (lit. 108−110 °C).32 Rf 0.30 in ethyl acetate−hexane
4-(Trifluoromethyl)nitrobenzene (8N).22 Yellow solid (164 mg,
1
86%), mp 40 °C (lit. 39−41 °C).22 Rf 0.72 in ethyl acetate−hexane
(2:8). H NMR (CDCl3) δ (ppm): 7.72−7.75 (m, 1H), 8.33 (d, J =
1
8.0 Hz, 1H), 8.51 (d, J = 8.0 Hz, 1H), 8.57 (d, J = 8.0 Hz, 1H), 8.81
(d, J = 8.4 Hz, 1H), 9.38 (s, 1H). 13C NMR (CDCl3) δ (ppm): 115.8,
126.0, 128.1, 128.6, 129.9, 135.0, 144.5, 146.5, 153.1.
(0.5:9.5). H NMR (CDCl3) δ (ppm): 7.86 (d, J = 8.8 Hz, 2H), 8.48
(d, J = 8.8 Hz, 2H). 13C NMR (CDCl3) δ (ppm): 121.7, 124.4 (q, J =
32 Hz), 127.5, 137.2 (q, J = 3 Hz), 150.3 (q, J = 260 Hz).
E
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5-Nitro-1,10-phenanthroline (19N).33 Light-yellow solid (183 mg,
AUTHOR INFORMATION
■
81%), mp 199−201 °C (lit. 200 °C).33 Rf 0.16 in ethyl acetate−hexane
1
Corresponding Author
*E-mail: pnataraj@pu.ac.in
(2:8). H NMR (CDCl3) δ (ppm): 7.77−7.83 (m, 2H), 8.42 (d, J =
8.4 Hz, 1H), 8.66 (s, 1H), 8.98 (d, J = 8.4 Hz, 1H), 9.29 (d, J = 4.8 Hz,
1H), 9.36 (d, J = 4.8 Hz, 1H). 13C NMR (CDCl3) δ (ppm): 120.7,
124.2, 124.3, 125.3, 125.4, 132.1, 137.8, 143.9, 145.9, 147.3, 151.4,
153.4.
Notes
The authors declare no competing financial interest.
2,2′-Dinitrobiphenyl (20N).34 Brown solid (203 mg, 83%), mp
121−122 °C (lit. 120−122 °C).34 Rf 0.32 in ethyl acetate−hexane
(1:9). 1H NMR (CDCl3) δ (ppm): 7.29−7.34 (m, 2H), 7.58−7.68 (m,
4H), 8.18−8.23 (m, 2 H). 13C NMR (CDCl3) δ (ppm): 124.7, 129.1,
131.0, 133.4, 134.2, 147.2.
ACKNOWLEDGMENTS
■
P.N. gratefully acknowledges the financial support of the
Department of Science & Technology (DST), India, through
INSPIRE Faculty Fellowship [IFA12-CH-62]. R.C. gratefully
acknowledges the junior research fellowship from the Council
of Scientific and Industrial Research (CSIR), New Delhi. In
addition, we thank the anonymous reviewers for their many
insightful comments and suggestions.
1,8-Dinitronaphthalene (21N).35 Brown solid (177 mg, 81%), mp
169−171 °C (lit. 171−172 °C).35 Rf 0.33 in ethyl acetate−hexane
1
(1:9). H NMR (CDCl3) δ (ppm): 7.92−7.97 (m, 2H), 8.51 (d, J =
8.4 Hz, 2H), 8.60 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3) δ (ppm):
115.1, 127.0, 127.4, 134.6, 134.8, 144.6.
2,7-Dinitro-9-fluorenone (22N).36 Brown solid (232 mg, 86%), mp
295 °C (lit. 296 °C).36 Rf 0.48 in ethyl acetate−hexane (2:8). 1H NMR
(CDCl3) δ (ppm): 7.89 (d, J = 8.0 Hz, 2H), 8.55−8.67 (m, 4H). 13C
NMR (CDCl3) δ (ppm): 119.5, 124.7, 131.5, 136.0, 147.8, 150.1,
190.8.
REFERENCES
■
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2-Methyl-2-nitropropane (23N).37 Light-yellow oil (82 mg, 79%).
Rf 0.94 in ethyl acetate−hexane (0.5:9.5). 1H NMR (CDCl3) δ (ppm):
1.62 (s, 9H). 13C NMR (CDCl3) δ (ppm): 27.9, 85.2.
Nitrocyclohexane (24N).38 Light-yellow oil (106 mg, 82%). Rf 0.91
in ethyl acetate−hexane (0.5:9.5). 1H NMR (CDCl3) δ (ppm): 1.09−
2.46 (m, 10H), 4.37−4.42 (m, 1H). 13C NMR (CDCl3) δ (ppm):
24.2, 24.8, 31.0, 84.7.
1-Nitroadamantane (25N).39 Pale-yellow solid (143 mg, 79%), mp
158−159 °C (lit. 159 °C).39 Rf 0.89 in ethyl acetate−hexane (0.5:9.5).
1H NMR (CDCl3) δ (ppm): 1.64−1.67 (m, 6H), 2.15 (s, 6H), 2.18 (s,
3H). 13C NMR (CDCl3) δ (ppm): 29.7, 35.5, 40.8, 84.7.
2-Methyl-2-nitrohexane (26N).40 Colorless oil (112 mg, 77%). Rf
1
0.92 in ethyl acetate−hexane (0.5:9.5). H NMR (CDCl3) δ (ppm):
0.83 (t, 3H), 1.18−1.52 (m, 10H), 1.99−2.01 (m, 2H). 13C NMR
(CDCl3) δ (ppm): 13.8, 19.8, 23.2, 25.5, 41.9, 88.2.
3-Nitropentane (27N).40 Pale-yellow oil (94 mg, 80%). Rf 0.92 in
ethyl acetate−hexane (0.5:9.5). 1H NMR (CDCl3) δ (ppm): 0.95 (t, J
= 7.2 Hz, 6H), 1.77−2.0 (m, 4H), 4.27−4.35 (m, 1H). 13C NMR
(CDCl3) δ (ppm): 10.3, 26.9, 91.9.
Nitrocyclopentane (28N).41 Colorless oil (90 mg, 78%). Rf 0.92 in
1
ethyl acetate−hexane (0.5:9.5). H NMR (CDCl3) δ (ppm): 1.65−
2.46 (m, 8H), 4.76−4.96 (m, 1H). 13C NMR (CDCl3) δ (ppm): 24.7,
32.6, 87.0.
2,3-Dimethyl-2,3-dinitrobutane (29N).42 Light-yellow solid (122
mg, 69%), mp 215 °C (lit. 214 °C).42 Rf 0.67 in ethyl acetate−hexane
(0.5:9.5). 1H NMR (CDCl3) δ (ppm): 2.76 (s, 12H). 13C NMR
(CDCl3) δ (ppm): 23.6, 92.8.
Fexinidazole (30N).43 Colorless solid (230 mg, 82%), mp 51−54
°C (lit. 50−54 °C).43 Rf 0.28 in ethyl acetate−hexane (2:8). 1H NMR
(CDCl3) δ (ppm): 2.42 (s, 3H), 3.91 (s, 3H), 5.28 (s, 2H), 7.01−7.09
(m, 2H), 7.21−7.30 (m, 2H), 8.07 (s, 1H). 13C NMR (CDCl3) δ
(ppm): 27.7, 30.6, 56.9, 117.9, 129.8, 131.0, 131.3, 142.9, 157.8, 161.8.
Nitazoxanide (31N).44 Light-yellow solid (218 mg, 71%), mp 200−
202 °C (lit. 202 °C).44 Rf 0.19 in ethyl acetate−hexane (2:8). 1H NMR
(CDCl3) δ (ppm): 2.29 (s, 3H), 7.24−7.31 (m, 1H), 7.37−7.46 (m,
1H), 7.60−7.68 (m, 1H), 7.81−7.86 (m, 1H), 8.56 (s, 1H). 13C NMR
(CDCl3) δ (ppm): 20.6, 123.2, 125.2, 125.6, 129.6, 133.2, 141.7, 142.2,
148.7, 161.9, 165.0, 168.6.
ASSOCIATED CONTENT
■
S
* Supporting Information
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2002, 124, 11250−11251. (b) Goossen, L. J.; Deng, G.; Levy, L. M.
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Rev. 2011, 40, 5010−5029. (d) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang,
S. Chem. Soc. Rev. 2011, 40, 5068−5083. (e) Shi, W.; Liu, C.; Lei, A.
Chem. Soc. Rev. 2011, 40, 2761−2776.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b02133.
1H and 13C spectra for all compounds prepared by the
method described (PDF)
F
DOI: 10.1021/acs.joc.5b02133
J. Org. Chem. XXXX, XXX, XXX−XXX

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