Basic ionic liquid as catalyst for the efficient and green synthesis of 2-amino-3-nitrobenzonitriles in ethanol

Article abstract of DOI:10.1080/00397911.2010.486503

A basic ionic liquid, [BmIm]OH was used as catalyst in the cyclocondensation of various kinds of vinylmalononitriles with nitroolefins in ethanol at reflux. A series of 2-amino-3-nitrobenzonitriles were obtained in reasonable yields. The straightforward and green protocol was found to be fairly efficient, and the catalyst could be recycled and reused in subsequent reactions with consistent activity. The mechanism of the reaction was discussed.

Full text of DOI:10.1080/00397911.2010.486503

This article was downloaded by: [University of Illinois at Urbana-Champaign]
On: 23 June 2013, At: 02:54
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Basic Ionic Liquid as Catalyst for the
Efficient and Green Synthesis of 2-
Amino-3-nitrobenzonitriles in Ethanol
Zhiwei Chen a , Kai Ding a & Weike Su a
a Key Laboratory of Pharmaceutical Engineering of Ministry of
Education, College of Pharmaceutical Sciences, Zhejiang University
of Technology, Hangzhou, China
Published online: 30 Mar 2011.
To cite this article: Zhiwei Chen , Kai Ding & Weike Su (2011): Basic Ionic Liquid as Catalyst for the
Efficient and Green Synthesis of 2-Amino-3-nitrobenzonitriles in Ethanol, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:10, 1410-1420
To link to this article: http://dx.doi.org/10.1080/00397911.2010.486503
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 41: 1410–1420, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.486503
BASIC IONIC LIQUID AS CATALYST FOR THE
EFFICIENT AND GREEN SYNTHESIS OF 2-AMINO-3-
NITROBENZONITRILES IN ETHANOL
Zhiwei Chen, Kai Ding, and Weike Su
Key Laboratory of Pharmaceutical Engineering of Ministry of Education,
College of Pharmaceutical Sciences, Zhejiang University of Technology,
Hangzhou, China
GRAPHICAL ABSTRACT
Abstract A basic ionic liquid, [BmIm]OH was used as catalyst in the cyclocondensation of
various kinds of vinylmalononitriles with nitroolefins in ethanol at reflux. A series of
2-amino-3-nitrobenzonitriles were obtained in reasonable yields. The straightforward and
green protocol was found to be fairly efficient, and the catalyst could be recycled and reused
in subsequent reactions with consistent activity. The mechanism of the reaction was
discussed.
Keywords 2-Amino-3-nitrobenzonitriles; catalyze; ionic liquid; vinylmalononitrile
Polysubstituted benzenes are important compounds in organic and natural
product chemistry. Likewise, as common structural units and frequently employed
synthetic precursors of many bioactive compounds,[1] they also play important roles
in medicinal chemistry.
Generally, using traditional routes of aromatic substitutions, such as Friedel–
Crafts reactions,[2] nucleophilic substitutions,[3] or coupling reactions,[4] it is difficult
to introduce amino and=or nitrile groups to given aromatics. Fortunately, some
methods have been developed to synthesize these multifunctionalized benzenes from
acyclic precursors using vinylmalononitriles as key starting materials.[5] However,
Received August 23, 2009.
Address correspondence to Weike Su, Key Laboratory of Pharmaceutical Engineering of Ministry
of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China.
E-mail: pharmlab@zjut.edu.cn
1410

2-AMINO-3-NITROBENZONITRILES
1411
Scheme 1. Synthetic protocol for 2-amino-3-nitrobenzonitriles.
these methods often suffer from certain drawbacks such as long procedures,
hazardous by-products, and use of equivalent or even excess amounts of alkali.
Therefore, how to synthesize polysubstituted benzenes efficiently and cleanly
remains a necessary problem to solve.
Ionic liquids, because of their unique properties such as noninflammability,
negligible vapor pressure, reusability, and high thermal stability,[6] have attracted
extensive research interest in the area of green chemistry in recent years. Moreover,
a task-specific basic ionic liquid, [BmIm]OH, has been successfully applied as a cata-
lyst to perform several classical organic reactions[7] and the synthesis of substituted
heterocycles such as pyrrole[8] and pyridine.[9] Recently, our group has reported a
simple and efficient synthetic protocol for polysubstituted benzenes using
Cu(OTf)2=Et3N as a novel catalytic system in CH3CN.[10] As part of our ongoing
interest in green chemistry, in this article, we introduce [BmIm]OH as a mild, highly
efficient, and environmentally benign catalyst for the preparation of substituted
2-amino-3-nitrobenzonitriles (Scheme 1). Additionally, one-pot synthesis of 2-
amino-3-nitrobenzonitriles was achieved via Knoevenagel condensation of ketone
with malononitrile and a sequential tandem reaction with nitroolefins (Scheme 2).
At the onset of this work, we investigated the appropriate loading amounts of
catalyst and selected the solvent with the model reaction of 1a with 2a using
[BmIm]OH as catalyst. The results are summarized in Table 1. It was found that
20 mol% of [BmIm]OH was enough to promote the reaction efficiently and the cata-
lyst could be reused three times without evident loss of activity (Table 1, entry 3). We
expected the reaction to perform in aqueous media, but probably as a result of the
poor solubility of the two starting materials in water, the result was disappointing
(Table 1, entry 6, 48%). Moreover, the solvent-free condition was also examined,
and a viscous reaction system and moderate yield were found (Table 1, entry 7,
Scheme 2. One-pot synthesis of 2-amino-3-nitrobenzonitriles from ketones.

1412
Z. CHEN, K. DING, AND W. SU
Table 1. Reaction of 1a and 2a under different conditionsa
Entry
[BmIm]OH (mol%)
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
10
15
EtOH
EtOH
EtOH
EtOH
EtOH
H2O
67
79
20
50
86, 79, 81c
82
81
48
67
80
100
20
20
—
—
[BmIm]OH
aThe reaction was carried out at 80 ꢀC or reflux for 4 h.
bYield of isolated product.
c[BmIm]OH was reused three times.
67%). EtOH was a better solvent (Table 1, entry 3, yield 86%) than other solvents
tested.
The subsequent study was performed under the optimized conditions: with 20 mol%
[BmIm]OH in ethanol at reflux, as described in Scheme 1. Most of the corresponding pro-
ducts, substituted 2-amino-3-nitrobenzonitriles 3, were obtained in good yields.
It was observed the process tolerated both electron-donating and electron-
withdrawing groups on phenyl when a series of substituted phenylethylidenemalono-
nitriles (Table 2, entries 1–7) were used to react with 2a. When phenyl was replaced
with furan-2-yl, the corresponding product was obtained in good yield (Table 2,
entry 8, 86% yield). We also attempted to use vinylmalononitriles with aliphatic
R1 and R2 to perform the reactions with 2a, which similarly gave the corresponding
products in satisfying yields (Table 2, entries 9–12). A cyclopropylbenzene frame-
work, which was difficult to prepare via aromatic subsitution, was constructed
expediently. Presumably as a result of steric hindrance, indeed, no reaction of 2-
(2-phenyl-1-p-tolylethylidene)malononitrile with 2a was observed under the same
conditions (Table 2, entry 15). Furthermore, a wide range of nitroolefins with differ-
ent R3 was reacted with 2-(1-phenylethylidene)malononitrile. Similar yields were
obtained irrespective of R3 being substituted phenyl, alkyl, and heterocycle
(Table 2, entries 16–21).
It was reported [BmIm]OH provides an efficient and convenient methodology
for the Knoevenagel condensation reaction between ketone and malononitrile.[7j]
The report inspired us to apply the one-pot strategy for the synthesis of 2-amino-3-
nitrobenzonitriles using ketones as starting materials (Scheme 2). As expectation,
catalyzed by [BmIm]OH in a minimum amount of EtOH at reflux, many ketones
reacted with malononitrile rapidly and afforded the corresponding vinylmalononi-
triles completely (monitored by thin-layer chromatography, TLC). Without further
purification, nitroolefins were then added to the reaction system to accomplish the
subsequent cyclocondensation. The products were obtained in moderate to good
yields based on ketones, as shown in the parentheses in Table 2.
In the reaction of 1a and 2a catalyzed by [BmIm]OH in EtOH, after stirring for
8 h at room temperature, the important intermediate, 2-(4-nitro-3-phenyl-1-p-tolyl-
butylidene)malononitrile 4a, was obtained (Scheme 3) in 90% yield. It suggested that

2-AMINO-3-NITROBENZONITRILES
1413
Table 2. [BmIm]OH-promoted synthesis of 2-amino-3-nitro benzonitriles in EtOH at refluxa
Entry
R1
R2
R3
Time (h)b
Product
Yield (%)c
1
2
3
4
5
6
7
8
4-MeC6H4
Ph
H
H
H
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4 (5.5)
4 (5.5)
3.5 (4.5)
5
3a
3b
3c
3d
3e
3f
86 (74)
84 (73)
88 (77)
79
4-MeOC6H4
4-FC6H4
4-ClC6H4
3-ClC6H4
3,4-(MeO)2C6H3
furan-2-yl
4.5
5
86
76
3 (4.5)
3 (4)
3g
3h
84 (72)
86 (75)
9
Ph
Ph
4 (6)
3i
3j
82 (70)
81 (72)
10
4 (4.5)
11
12
Ph
Ph
4 (4.5)
3k
3l
81 (73)
80 (68)
H
4.5 (5.5)
13
14
15
16
17
18
19
20
Ph
3-ClC6H4
4-MeC6H4
Ph
Me
Me
Ph
H
Ph
Ph
5
5.5
3m
3n
/
72
64
Ph
6
0
furan-2-yl
thien-2-yl
4-MeOC6H4
3-MeOC6H4
3-NO2C6H4
4 (5.5)
4 (5.5)
4 (5.5)
4 (5.5)
4 (5.5)
3o
3p
3q
3r
3s
85 (73)
84 (70)
85 (71)
83 (68)
82 (70)
Ph
Ph
H
H
Ph
Ph
H
H
21
Ph
H
4 (5.5)
3t
84 (72)
aAll reactions were carried out on a 1 mmol vinylmalononitriles with 1 mmol nitroolefins in the presence
of 0.2 mmol [BmIm]OH in EtOH (3 mL) at reflux.
bReaction time of one-pot synthesis of 2-amino-3-nitro benzonitriles from ketones (in bracket).
cIsolated yields based on vinylmalononitrles and yields of one-pot synthesis of 2-amino-3-nitro benzoni-
triles based on ketones (in bracket).
the reaction pass through an ionic mechanism. With all these results in hand, we
propose a plausible mechanism for [BmIm]OH catalyzed synthesis of 2-amino-3-
nitrobenzonitriles in Scheme 4.
In summary, a new catalytic protocol to synthesize 2-amino-3-nitrobenzoni-
triles via the cyclocondensation of various vinylmalonitriles and nitroolefins has been

1414
Z. CHEN, K. DING, AND W. SU
Scheme 3. Preparation of important intermediate 4a.
Scheme 4. Plausible mechanism.
developed. [BmIm]OH was efficient to promote a one-pot synthesis of 2-amino-3-
nitrobenzonitriles via Knoveangal condensation reaction of ketone and malononi-
trile and a sequential tandem reaction with nitroolefins. Compared with previously
reported methodelogies, the attractive features of the present process are simple
workup, short reaction time, environmentally benign solvent, reusability of basic
ionic [BmIm]OH, and its adaptability for the synthesis of a broad range of polysub-
stituted 2-amino-3-nitrobenzonitriles in good yields.
EXPERIMENTAL
1
Melting points are uncorrected. HNMR and 13CNMR spectra were recorded
on Varian 400 or 500 instruments using tetramethylsilane (TMS) as internal stan-
dard. Mass spectroscopy (MS) data of the products were collected on a MS–EI
instrument (Finnigan Trace DSQ). Infrared (IR) spectra were collected on a Nicolet
2100 IR spectrometer. All reactions were monitored by TLC with GF254 silica-gel-
coated plates. Starting materials and solvents were purchased from common
commercial sources or prepared via common method without further purification.

2-AMINO-3-NITROBENZONITRILES
1415
The reaction mixture was purified by column chromatography over silica gel (200–
300 mesh). The synthesis of this basic ionic liquid was prepared as previously
described.[7f]
Typical Procedure for the Preparation of 2-Amino-3-
nitrobenzonitriles
Vinylmalononitile (1 mmol), nitroolefin (1 mmol), and [BmIm]OH (0.2 mmol,
18 mg) were dissolved in a minimum amount (1 mL) of ethanol to carry out the reac-
tion in a solution phase. The reaction mixture was stirred at reflux temperature for
the desired time. After the completion of the reaction (monitored by TLC), EtOAc
(15 mL) was added to dilute the reaction solution. Then the mixture was washed with
water. The combined organic phases were dried and concentrated in vacuo, purified
by column chromatography [silica gel, hexane=AcOEt (v=v) ¼ 8:1] to afford the
2-amino-3-nitrobenzonitrile 3. The products could be easily identified by the singlet
1
peak of the amido in H NMR spectra. The residue aqueous phase was evaporated
under reduced pressure, and the remaining [BmIm]OH was rinsed with ethyl acetate,
dried under a vacuum, and reused for three runs.
Typical Procedure for the One-Pot Synthesis of 2-Amino-3-
nitrobenzonitriles from Ketones
A minimum amount (1 mL) of ethanol was added to a mixture of ketone
(1 mmol), malononitrile (1 mmol), and [BmIm]OH (0.2 mmol, 18 mg) to carry out
the reaction in a solution phase. The reaction mixture was stirred at reflux tempera-
ture and monitored by TLC. When vinylmalononitrile was obtained completely,
without further purification, nitroolefins (1 mmol) were then added to the reaction
system and stirred for the desired time to accomplish the subsequent cyclocondensa-
tion. After the completion of the reaction (monitored by TLC), EtOAc (15 mL) was
added to dilute the reaction solution. Then the mixture was washed with water. The
combined organic phases were dried and concentrated in vacuo and purified by
column chromatography [silica gel, hexane=AcOEt (v=v) ¼ 8:1] to afford the
2-amino-3-nitrobenzonitrile 3.
Selected Data
Compound 3a. Yellow crystals; mp 196–198 ꢀC; yield: 86%. 1H NMR
(400 MHz, CDCl3) d 7.42–7.49 (5H, m, ArH), 7.26–7.34 (4H, m, ArH), 6.80 (1H,
s, ArH), 5.88 (2H, s, NH2), 2.43 (3H, s, CH3). MS (EI): m=z (%) ¼ 330 (35,
Mþ þ 1), 329 (Mþ, 100). HRMS (EI) calcd. for C20H15N3O2 ([M]þ) 329.1164; found:
329.1162.
Compound 3b. Mp 202–203 ꢀC (lit.[5a] 204.2–205.8 ꢀC); yield: 84% (lit.[5a]
76%). 1HNMR (500 MHz, CDCl3) d 7.57–7.59 (2H, m, ArH), 7.50 (2H, dd,
J12.0 Hz, J2 5.5 Hz, ArH), 7.43 (3H, dd, J12.0 Hz, J2 5.5 Hz, ArH), 7.32–7.34 (2H,
m, ArH), 6.81 (1H, s, ArH), 5.87 (2H, s, NH2). 13CNMR (125 MHz, CDCl3) d

1416
Z. CHEN, K. DING, AND W. SU
149.5, 144.8, 143.0, 137.3, 137.0, 130.0, 129.0, 128.4, 127.2, 115.8, 97.7. MS (EI): m=z
(%) ¼ 315 (Mþ, 52), 77 (100).
Compound 3c. Yellow crystals; mp 191–192 ꢀC; yield: 88%. 1H NMR
(500 MHz, CDCl3) d 7.55 (2H, dd, J1 2.0 Hz, J2 6.8 Hz, ArH), 7.43–7.45 (3H, m,
ArH), 7.32–7.34 (2H, m, ArH), 7.02 (2H, dd, J1 2.0 Hz, J2 6.8 Hz, ArH), 6.78 (1H,
s, ArH), 5.91 (2H, s, NH2), 3.87 (3H, s, OCH3). 13CNMR (125 MHz, CDCl3) d
161.0, 149.3, 145.0, 143.0, 137.5, 133.7, 129.9, 129.2, 128.9, 128.8, 127.2, 126.3,
121.1, 116.2, 114.4, 92.3, 55.4. MS (EI) m=z (%) ¼ 345 (Mþ, 44), 114 (100). HRMS
(EI) calcd. for C20H15N3O3 ([M]þ) 345.1113; found: 345.1112.
Compound 3d. Yellow crystals; mp 193–194 ꢀC; yield: 79%. 1H NMR
(500 MHz, CDCl3) d 7.56–7.59 (2H, m, ArH), 7.43 (3H, dd, J1 4.0 Hz, J2 6.0 Hz,
ArH), 7.33 (2H, dd, J1 2.5 Hz, J2 6.0 Hz, ArH), 7.21 (2H, q, J 9.0 Hz, ArH), 6.77
(1H, s, ArH), 5.87 (2H, s, NH2); 13C NMR (125 MHz, CDCl3) d 163.8 (J 311 Hz),
148.4, 144.8, 143.1, 137.2, 134.4, 129.0, 127.2, 121.1, 116.2, 116.0, 115.7, 97.7. IR
(KBr) nmax: 3481, 3373, 2216, 1502, 1280, 837, 770. MS (EI) m=z (%) ¼ 334
(Mþ þ 1, 7), 333 (Mþ, 30), 59 (100). HRMS (EI) calcd. for C19H12FN3O2 ([M]þ)
333.0914; found: 333.0915.
Compound 3e. Yellow crystals; mp 183–184 ꢀC; yield: 82%. 1H NMR
(500 MHz, CDCl3) d 7.47–7.53 (4H, m, ArH), 7.42–7.45 (3H, m, ArH), 7.31–7.33
(2H, m, ArH), 6.77 (1H, s, ArH), 5.86 (2H, s, NH2). 13C NMR (125 MHz, CDCl3)
d 148.1, 144.8, 143.1, 137.1, 136.2, 135.4, 134.5, 129.8, 129.2, 129.0, 128.9, 127.2,
121.0, 115.6, 97.6. IR (KBr) nmax: 3467, 3354, 2217, 1497, 1097. MS (EI) m=z
(%) ¼ 349 (Mþ, 100). HRMS (EI) calcd. for C19H12ClN3O2 ([M]þ) 349.0618; found:
349.0619.
Compound 3f. Yellow crystals; mp 180–181 ꢀC; yield: 76%. 1H NMR
(400 MHz, CDCl3) d 7.53 (1H, d, J 1.6 Hz, ArH), 7.44–7.51 (6H, m, ArH),
7.32–7.34 (2H, m, ArH), 6.79 (1H, s, ArH), 5.86 (2H, s, NH2). 13C NMR
(100 MHz, CDCl3) d 149.2, 145.9, 143.9, 138.1, 137.2, 135.0, 134.5, 128.6, 129.5,
129.0 (2C), 127.2, 121.6, 116.1, 98.2. IR (KBr) nmax: 3511, 3372, 2224, 1505, 1088.
MS (EI) m=z (%) ¼ 349 (Mþ, 100). HRMS (EI) calcd. for C19H12ClN3O2 ([M]þ)
349.0618; found: 349.0615.
Compound 3g. Yellow crystals; mp 176–177 ꢀC; yield: 84%. 1H NMR
(400 MHz, CDCl3) 7.43–7.45 (3H, m, ArH), 7.34 (1H, t, J 3.6 Hz, ArH), 7.32 (1H,
s, ArH), 7.19 (1H, dd, J1 2.0 Hz, J2 8.4 Hz, ArH), 7.11 (1H, d, J 3.0 Hz, ArH),
6.98 (1H, d, J 3.0 Hz, ArH), 6.81 (1H, s, ArH), 5.90 (2H, s, NH2), 3.95 (6H, s,
OCH3). 13CNMR (100 Hz, CDCl3) d 150.6, 149.3, 149.2, 145.0, 143.0, 137.5,
133.8, 129.5, 128.9 (2C), 127.2, 121.5, 121.0, 116.1, 111.6, 111.4, 97.4, 56.1, 56.0.
MS (EI) m=z (%) ¼ 376 (Mþ þ 1, 19), 375 (Mþ, 100). HRMS (EI) calcd. for
C21H17N3O4 ([M]þ) 375.1219; found: 375.1213.
3-Amino-5-(furan-2-yl)-2-nitrobiphenyl-4-carbonitrile (3h). Yellow crys-
tals; mp 188–189 ꢀC (lit.[5a] 188.4–191.2 ꢀC); yield: 86% (lit.[5a] 67%). 1H NMR
(500 MHz, CDCl3) d 7.61 (1H, s, ArH), 7.44 (4H, t, J 2.5 Hz, ArH), 7.33–7.34
(2H, t, ArH), 7.20 (1H, s, ArH), 6.61 (1H, d, J 1 Hz, ArH), 5.96 (2H, s, NH2).
13C NMR (125 MHz, CDCl3) d 148.7, 145.4, 144.9, 143.5, 137.6, 136.2, 133.3,

2-AMINO-3-NITROBENZONITRILES
1417
128.9, 128.8, 127.1, 117.1, 116.2, 113.4, 113.0. MS (EI) m=z (%) ¼ 306 (Mþ þ 1, 30),
305 (Mþ, 100). IR (KBr) nmax: 3467, 3363, 2212, 1571, 1553, 1494, 1483, 759. HRMS
(EI) calcd. for C17H11N3O3 ([M]þ) 305.0800; found: 305.0802.
3-Amino-2-nitro-1-phenyl-9,10-dihydrophenanthrene-4-carbonitrile (3i).
1
Yellow crystals; mp 201–202 ꢀC (lit.[5a] 201.2–203.4 ꢀC); yield: 82% (lit.[5a] 71%). H
NMR (500 MHz, CDCl3) d 8.24 (1H, t, J 2.0 Hz, ArH), 7.40–7.47 (5H, m, ArH),
7.28 (1H, dd, J1 6.5 Hz, J2 8.5 Hz, ArH), 7.20–7.22 (2H, m, ArH), 5.66 (2H, s,
NH2), 2.64 (2H, q, J 5.0 Hz, CH2CH2), 2.39 (2H, q, J 5.0 Hz, CH2CH2). 13C
NMR (125 MHz, CDCl3) d 143.3, 142.5, 140.4, 139.8, 135.7, 131.1, 130.5, 128.8,
128.6, 128.0, 127.9, 127.4, 127.1, 117.2, 95.4, 29.1, 26.0. IR (KBr) nmax: 3466,
3382, 2214, 1620, 1512, 920, 706. MS (EI) m=z (%) ¼ 341 (Mþ, 54), 305 (100).
2-Amino-3-nitro-4-phenyl-5,6,7,8-tetrahydronaphthalene-1-carbonitrile
(3j). Mp 209–210 ꢀC (lit.[5a] 211.2–214.3 ꢀC); yield: 81% (lit.[5a] 62%). 1H NMR
(500 MHz, CDCl3) d 7.37–7.43 (3H, m, ArH), 7.14 (2H, d, J 7.5 Hz, ArH), 5.35
(2H, s, NH2), 2.96 (2H, t, J 7.5 Hz, CH2), 2.23 (2H, t, J 7.5 Hz, CH2), 1.77–1.82
(2H, m, CH2), 1.62–1.67 (2H, m, CH2). IR (KBr) nmax: 3463, 3357, 2940, 2220,
1518. MS (EI) m=z (%) ¼ 294 (Mþ þ 1, 15), 293 (Mþ, 100).
5-Amino-6-nitro-7-phenyl-2,3-dihydro-1H-indene-4-carbonitrile
(3k).
Yellow crystals; mp 197–198 ꢀC; yield: 81%. 1H NMR (400 MHz, CDCl3) d
7.36–7.44 (3H, m, ArH), 7.18–7.21 (2H, m, ArH), 5.61 (2H, s, NH2), 3.12 (2H, t,
J 3.6 Hz, CH2), 2.65 (2H, t, J 3.6 Hz, CH2), 2.05–2.12 (2H, m, CH2). 13C NMR
(100 MHz, CDCl3) d 153.8, 143.1, 138.8, 136.3, 133.9, 128.7, 128.3, 127.2, 115.1,
95.4, 33.9, 32.0, 29.7. IR (KBr) nmax: 3475, 3362, 2923, 2220, 1513. MS (EI) m=z
(%) ¼ 280 (Mþ þ 1, 18), 279 (Mþ, 100). HRMS (EI) calcd. for C16H13N3O2 ([M]þ)
279.1008; found: 279.1012.
3-Amino-5-cyclopropyl-2-nitrobiphenyl-4-carbonitrile (3l). Yellow crys-
1
tals; mp 164–165 ꢀC; yield: 81%. H NMR (500 MHz, CDCl3) d 7.40–7.42 (3H, m,
ArH), 7.23–7.26 (2H, m, ArH), 6.12 (1H, s, ArH), 5.85 (2H, s, NH2), 2.24–2.29
(1H, m, CH), 1.21–1.25 (2H, m, CH2), 0.88–0.91 (2H, m, CH2). 13C NMR
(125 MHz, CDCl3) d 153.7, 144.4, 143.5, 138.0, 128.9, 127.1, 115.3, 115.2, 99.3,
15.1, 10.8. MS (EI) m=z (%) ¼ 280 (Mþ þ 1, 18), 279 (Mþ, 100). HRMS (EI) calcd.
for C16H13N3O2 ([M]þ) 279.1008; found: 279.1010.
Compound 3m. Yellow crystals; mp 171–172 ꢀC; yield: 72%. 1H NMR
(500 MHz, CDCl3) d 7.39–7.52 (6H, m, ArH), 7.29–7.31 (2H, m, ArH), 7.21–7.23
(2H, m, ArH), 5.36 (2H, s, NH2), 1.71 (3H, s, CH3). 13C NMR (125 MHz, CDCl3)
d 149.6, 141.7, 141.1, 137.4, 138.6, 136.0, 129.0, 128.9, 128.7, 128.5, 128.1, 125.6,
115.5, 100.8, 17.9. MS (EI) m=z (%) ¼ 330 (Mþ þ 1, 22), 329 (Mþ, 100). HRMS
(EI) calcd. for C20H15N3O2 ([M]þ) 329.1164; found: 329.1169.
Compound 3n. Yellow crystals; mp 164–165 ꢀC; yield: 64%. 1H NMR
(500 MHz, CDCl3) d 7.41–7.46 (5H, m, ArH), 7.31 (1H, d, J 0.5 Hz, ArH),
7.19–7.22 (3H, m, ArH), 5.36 (2H, s, NH2), 1.72 (3H, s, CH3). 13C NMR
(125 MHz, CDCl3) d 147.8, 141.9, 139.1, 137.1, 135.6, 134.9, 130.3, 129.3, 128.8,
128.1, 127.9, 126.7, 125.5, 115.2, 110.0, 59.5. IR (KBr) nmax: 3463, 3353, 2223,

1418
Z. CHEN, K. DING, AND W. SU
1513. MS (EI) m=z (%) ¼ 363 (Mþ, 18), 94 (100). HRMS (EI) calcd. for
C20H14ClN3O2 ([M]þ) 363.0775; found: 363.0773.
3-Amino-5-(furan-2-yl)-4-nitrobiphenyl-2-carbonitrile (3o). Yellow crys-
1
tals; mp 164–165 ꢀC; yield: 85%. H NMR (500 MHz, CDCl3) d 7.50–7.58 (5H, m,
ArH), 7.26 (1H, s, ArH), 7.05 (1H, s, ArH), 6.76 (1H, d, J 3.2 Hz, ArH), 6.53
(1H, dd, J1 2.0 Hz, J2 3.2 Hz, ArH), 6.58 (2H, s, NH2). 13C NMR (125 MHz, CDCl3)
d 117.0, 110.7, 107.3, 106.7, 99.5, 92.3, 92.1, 90.9, 80.5, 78.2, 74.8, 74.1. MS (EI) m=z
(%) ¼ 305 (Mþ, 23), 232 (100). HRMS (EI) calcd. for C17H11N3O3 ([M]þ) 305.0800;
found: 305.0801.
3-Amino-4-nitro-5-(thiophen-2-yl)biphenyl-2-carbonitrile (3p). Yellow
crystals; mp 171–172 ꢀC; yield: 84%. 1H NMR (500 MHz, CDCl3) d 7.56–7.58
(2H, m, ArH), 7.50–7.53 (3H, m, ArH), 7.46 (1H, dd, J1 2.0 Hz, J2 5.0 Hz, ArH),
7.08–7.13 (2H, m, ArH), 6.92 (1H, s, ArH), 5.65 (2H, s, NH2). MS (EI) m=z
(%) ¼ 322 (Mþ þ 1, 23), 321 (Mþ, 100). HRMS (EI) calcd. for C17H11N3O2S
([M]þ) 321.0572; found: 321.0575.
Compound 3q. Yellow crystals; mp 172–173 ꢀC (lit.[5a] 167.2–169.3 ꢀC); yield:
85% (lit.[5a] 61%). 1H NMR (500 MHz, CDCl3) d 7.56–7.58 (2H, m, ArH), 7.48–7.51
(2H, m, ArH), 7.26–7.29 (2H, m, ArH), 6.94–6.97 (2H, m, ArH), 6.80 (1H, s, ArH),
5.77 (2H, s, NH2), 3.84 (3H, s, OCH3); 13C NMR (125 MHz, CDCl3) d 160.3, 149.3,
144.7, 142.4, 137.1, 134.5, 129.8, 129.3, 128.9, 128.6, 128.4, 131.1, 116.4, 114.5, 97.2,
55.4. MS (EI) m=z (%) ¼ 345 (Mþ, 38), 114 (100). HRMS (EI) calcd. for C20H15N3O3
([M]þ) 345.1113; found: 345.1111.
Compound 3r. Yellow crystals; mp 190–191 ꢀC; yield: 83%. 1H NMR
(400 MHz, CDCl3) d 7.49–7.59 (5H, m, ArH), 7.33 (1H, t, J 8.0 Hz, ArH),
6.86–6.96 (3H, m, ArH), 6.60 (1H, s, ArH), 5.85 (2H, s, NH2), 3.81 (3H, s,
OCH3); 13C NMR (100 MHz, CDCl3) d 159.8, 149.4, 144.7, 142.7, 138.5, 137.0,
134.3, 130.0, 129.9, 128.9, 128.4, 121.0, 119.5, 115.7, 114.3, 113.0, 97.7, 55.3. MS
(EI) m=z (%) ¼ 346 (Mþ þ 1, 24), 345 (Mþ, 100). HRMS (EI) calcd. for
C20H15N3O3 ([M]þ) 345.1113; found: 345.1104.
Compound 3s. Yellow crystals; mp 218–219 ꢀC; yield: 82%. 1H NMR
(500 MHz, CDCl3) d 8.30 (1H, d, J 2.5 Hz, ArH), 8.23 (1H, s, ArH), 7.58–7.63
(4H, m, ArH), 7.53 (3H, t, J 3.0 Hz, ArH), 6.78 (1H, s, ArH), 6.21 (2H, s, NH2);
13C NMR (125 MHz, CDCl3) d 149.1, 144.3, 137.1, 136.8, 134.7, 129.9, 129.0,
128.4, 128.1, 127.4, 121.3, 115.7, 97.8. IR (KBr) nmax: 3464, 3358, 2217, 1536,
1492. MS (EI): m=z (%) ¼ 361 (Mþ þ 1, 21), 360 (Mþ, 100). HRMS (EI) calcd. for
C19H12N4O4 ([M]þ) 360.0859; found: 360.0867.
3-Amino-5-cyclohexyl-4-nitrobiphenyl-2-carbonitrile (3t). Yellow crys-
1
tals; mp 167–168 ꢀC; yield: 84%. H NMR (400 MHz, CDCl3) d 7.48–7.55 (5H, m,
ArH), 6.80 (1H, s, ArH), 5.48 (2H, s, ArH), 2.76–2.82 (1H, m, CH), 1.78–1.93 (m,
5H), 1.22–1.46 (m, 5H). 13C NMR (100 MHz, CDCl3) d 148.9, 148.0, 143.9, 137.6,
135.9, 129.5, 128.8, 128.4, 120.1, 117.8, 115.9, 96.1, 68.6, 40.3, 37.2, 33.7, 26.4,
25.8. MS (EI) m=z (%) ¼ 321 (Mþ, 7), 304 (100). HRMS (EI) calcd. for
C19H19N3O2 ([M]þ) 321.1477; found: 321.1481.

2-AMINO-3-NITROBENZONITRILES
1419
2-(4-Nitro-1,3-diphenylbutylidene)malononitrile (4a). White crystals; mp
1
101–102 ꢀC; yield: 90%. H NMR (400 MHz, CDCl3) d 7.31–7.34 (5H, m, ArH),
7.20–7.26 (2H, m, ArH), 6.96–6.99 (2H, m, ArH), 4.52–4.65 (2H, m, CH2NO2),
3.36–3.46 (3H, m, CH2CH), 2.45 (3H, s, CH3). 13C NMR (100 MHz, CDCl3):
d ¼ 175.4, 143.7, 135.5, 130.5, 130.1, 129.3, 128.8, 127.7, 127.5, 112.5, 85.9, 79.1,
42.8, 39.9, 21.6. MS (EI): m=z (%) ¼ 331 (Mþ, 2), 104 (100). HRMS (EI) calcd. for
C20H17N3O2 ([M]þ) 331.1321; found: 331.1316.
ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of China (Nos.
20676123 and 20876147) for financial support.
REFERENCES
1. Recent selected examples: (a) Warshakoon, N. C.; Sheville, J.; Bhatt, R. T.; Ji, W.;
Mendez-Andino, J. L.; Meyers, K. M.; Kim, N.; Wos, J. A.; Mitchell, C.; Paris, J. L.;
Pinney, B. B.; Reizes, O.; Hu, X. E. Design and synthesis of substituted quinolines as
novel and selective melanin-concentrating hormone antagonists as anti-obesity agents.
Bioorg. Med. Chem. Lett. 2006, 16, 5207–5211; (b) Frazier, K.; Jazan, E.; McBride, C.
M.; Pecchi, S.; Renhowe, P. A.; Shafer, C. M.; Taylor, C.; Bussiere, D.; He, M. M.;
Jansen, J. M.; Lapointe, M.; Ma, S.; Vora, J.; Wiesmann, J. Design and structure–activity
relationship of heterocyclic analogs of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-one
as inhibitors of receptor tyrosine kinases. Bioorg. Med. Chem. Lett. 2006, 16, 2247–
2251; (c) Wang, J. Q.; Gao, M.; Miller, K. D.; Sledge, G. W.; Zheng, Q.-H. Synthesis
of [11C]Iressa as a new potential PET cancer imaging agent for epidermal growth factor
receptor tyrosine kinase. Bioorg. Med. Chem. Lett. 2006, 16, 4102–4106; (d) Nakamura,
H.; Sasaki, Y.; Uno, M.; Yoshikawa, T.; Asano, T.; Ban, H. S.; Fukazawa, H.; Shibuya,
M.; Uehara, Y. Synthesis and biological evaluation of benzamides and benzamidines as
selective inhibitors of VEGFR tyrosine kinases. Bioorg. Med. Chem. Lett. 2006, 16,
5127–5131; (e) Kaiah, T.; Lingaiah, B. P. V.; Narsaiah, B.; Shireesha, B.; Kumar, B.
A.; Gururaj, S.; Pathasarathy, T.; Sridhar, B. Synthesis and structure–activity relation-
ships of novel pyrimido[1,2-b]indazoles as potential anticancer agents against A-549 cell
lines. Bioorg. Med. Chem. Lett. 2007, 17, 3445–3453; (f) Romagnoli, R.; Baraldi, P. G.;
Carrion, M. D.; Cara, G. L.; Preti, D.; Fruttarolo, F.; Parani, M. G.; Tabrizi, M. A.;
Tolomeo, M.; Grimando, S.; Cristina, A. D.; Balazarini, J.; Hadfield, J. A.; Brancale,
A.; Hamel, E. Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene
derivatives as antimitotic agents and inhibitors of tubulin polymerization. J. Med. Chem.
2007, 50, 2273–2277.
2. (a) Olah, G. Friedel–Crafts and Related Reactions; Wiley Interscience: New York, 1963;
vols. I–IV; (b) Pearson, D. E.; Buehler, C. A. Friedel–Crafts acylation with little or no
catalyst. Synthesis 1972, 533–542.
3. Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Aryl–aryl bond formation
one century after the discovery of the Ullmann reaction. Chem. Rev. 2002, 102, 1359–1469.
4. Saito, S.; Yamamoto, Y. Recent advances in the transition-metal-catalyzed regioselective
approaches to polysubstituted benzene derivatives. Chem. Rev. 2000, 100, 2901–2915.
5. (a) Xue, D.; Li, J.; Zhang, Z.-T.; Deng, J.-G. Efficient method for the synthesis of poly-
substituted benzenes by one-pot tandem reaction of vinyl malononitriles with nitroolefins.
J. Org. Chem. 2007, 72, 5443–5445; (b) Milart, P.; Wilamowski, J.; Sepiol, J.-J. Synthesis

1420
Z. CHEN, K. DING, AND W. SU
of di- and triamino-l,l0:30,l00-terphenyls from arylethylidene- and arylidenemalonodini-
triles. Tetrahedron 1998, 54, 15643–15656; (c) Wang, X. S.; Zhang, M. M.; Li, Q.; Yao,
C. S.; Tu, S. J. An improved and clean procedure for the synthesis of one-donor poly-
acceptors systems containing 2,6-dicyanoamine moiety in aqueous media catalyzed by
TEBAC in the presence and absence of K2CO3. Tetrahedron 2007, 63, 5265–5273.
6. (a) Cammarata, L.; Kazarian, S. G.; Salter, P. A.; Welton, T. Molecular states of water in
room temperature ionic liquids. Phys. Chem. Chem. Phys. 2001, 3, 5192–5200; (b) Kamal,
A.; Chouhan, G. Investigations towards the chemoselective thioacetaliztion of carbonyl
compounds by using ionic liquid [bmim]Br as a recyclable catalytic medium. Adv. Synth.
Catal. 2004, 346, 579–582.
7. (a) Raru, B. C.; Jana, R. Ionic liquid as catalyst and reaction medium—A simple, efficient,
and green procedure for Knoevenagel condensation of aliphatic and aromatic carbonyl
compounds using a task-specific basic ionic liquid. Eur. J. Org. Chem. 2006, 3767–3770;
(b) Xu, J. M.; Wu, Q.; Zhang, Q. Y.; Zhang, F.; Lin, X. F. A basic ionic liquid as catalyst
and reaction medium: A rapid and simple procedure for aza-Michael addition reactions.
Eur. J. Org. Chem. 2007, 1798–1802; (c) Tsogoeva, S. B.; Jagtap, S. B.; Ardemasova, Z. A.;
Kalikhevich, V. N. Trends in asymmetric Michael reactions catalysed by tripeptides in
combination with an achiral additive in different solvents. Eur. J. Org. Chem. 2004,
4014–4019; (d) Raru, B. C.; Banerjee, S. Ionic liquid as catalyst and solvent: The remark-
able effect of a basic ionic liquid, [bmIm]OH, on Michael addition and alkylation of active
methylene compounds. Tetrahedron 2007, 63, 776–782; (e) Yang, L.; Xu, L. W.; Zhou, W.;
Li, L.; Xia, C. G. Highly efficient aza-Michael reactions of aromatic amines and
N-heterocycles catalyzed by a basic ionic liquid under solvent-free conditions. Tetrahedron
Lett. 2006, 47, 7723–7726; (f) Raru, B. C.; Banerjee, S. Ionic liquid as catalyst and reaction
medium: The dramatic influence of a task-specific ionic liquid, [bmIm]OH, in Michael
addition of active methylene compounds to conjugated ketones, carboxylic esters, and
nitriles. Org. Lett. 2005, 7, 3049–3052; (g) Xu, J. M.; Liu, B. K.; Wu, W. B.; Qian, C.;
Lin, X. F. Basic ionic liquid as catalysis and reaction medium: A novel and green protocol
for the Markovnikov addition of N-heterocycles to vinyl esters, using a task-specific ionic
liquid, [bmIm]OH. J. Org. Chem. 2006, 71, 3991–3993; (h) Sun, H.; Zhang, D.; Wang, F.;
Liu, C. Theoretical study of the mechanism for the Markovnikov addition of imidazole to
vinyl acetate catalyzed by the ionic liquid [bmIm]OH. J. Phys. Chem. A. 2007, 111, 4535–
4541; (i) Wu, H.; Zhang, F. R.; Wan, Y.; Ye, L. An efficient protocol for Henry reaction
using basic ionic liquid [bmIm]OH as catalyst and reaction medium. Lett. Org. Chem.
2008, 5, 209–211; (j) Yadav, L. D.; Rai, A. The first ionic liquid-promoted three-
component coupling strategy for an expeditious synthesis of b-nitrocarbonitriles=
thiocyanates. Tetrahedron Lett. 2009, 50, 640–643; (k) Gong, K.; Fang, D.; Wang,
H. L.; Liu, Z. L. Basic functionalized ionic liquid–catalyzed one-pot Mannich-type reac-
tion: Three-component synthesis of b-amino carbonyl compounds. Monatsh. Chem. 2007,
138, 1195–1198.
8. Raru, B. C.; Banerjee, S.; Sowmiah, S. An improved procedure for the three-component
synthesis of highly substituted pyridines using ionic liquid. J. Org. Chem. 2007, 72,
3152–3154.
9. Yavari, I.; Kowsari, E. Task-specific basic ionic liquid: A reusable and green catalyst for
one-pot synthesis of highly functionalized pyrroles in aqueous media. Synlett. 2008, 6,
897–899.
10. Su, W. K.; Ding, K.; Chen, Z. W. Cu(OTf)2=Et3N-promoted cyclocondensation of acti-
vated a-methylene alkenes and nitroolefins: A novel one-pot synthesis of polysubstituted
benzenes. Tetrahedron Lett. 2009, 50, 636–639.