A novel synthesis of 3-aryl-2,6-dicyano-5-methylanilines via reaction between nitrostyrenes and malononitrile

Article abstract of DOI:10.1055/S-0029-1218717

A novel and simple synthesis of 3-aryl-2,6-dicyano-5-methylanilines is described. Reactions between nitrostyrenes and excess malononitrile in the presence of sodium carbonate in 80% ethanol proceeded at room temperature to afford the aromatic products in good yields. A mechanism for the formation of the products is proposed. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/S-0029-1218717

1526
PAPER
A Novel Synthesis of 3-Aryl-2,6-dicyano-5-methylanilines via Reaction
between Nitrostyrenes and Malononitrile
S
ynthesis of 3-Aryl-2,6
e
-
dicyano-5
h
-methylanilin
d
e
s
i Adib,*a Bagher Mohammadi,a Samira Ansari,a Hamid R. Bijanzadeh,b Long-Guan Zhuc
a
School of Chemistry, University College of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran
Fax +98(21)66495291; E-mail: madib@khayam.ut.ac.ir
b
c
Department of Chemistry, Tarbiat Modarres University, P.O. Box 14115-175, Tehran, Iran
Chemistry Department, Zhejiang University, Hangzhou 310027, P. R. of China
Received 12 October 2009; revised 13 January 2010
2,6-Dicyanoanilines are typically prepared from
(arylidene)malononitriles and (1-arylethylidene)malono-
nitriles in the presence of a base.11 Other synthetic routes
include: reaction of malononitrile and a,b-unsaturated ke-
Abstract: A novel and simple synthesis of 3-aryl-2,6-dicyano-5-
methylanilines is described. Reactions between nitrostyrenes and
excess malononitrile in the presence of sodium carbonate in 80%
ethanol proceeded at room temperature to afford the aromatic prod-
ucts in good yields. A mechanism for the formation of the products tones,12 one-pot tandem reaction of (alkylidene)malononi-
triles with nitroolefins in the presence of a base,13 reaction
is proposed.
of ynones and malononitrile,14 reaction of a-methylene
Key words: 2,6-dicyanoanilines, nitrostyrenes, aromatics, regio-
ketones or enamino ketones with malononitrile,15 ring-
selective, cyclizations
transformation of functionalized 2H-pyran-2-ones with
malononitrile,16 the three-component reaction of alde-
hydes, ketones and malononitrile under solvent-free
conditions17 or microwave irradiation,18 and reaction be-
tween (arylidene)malononitriles, dialkyl acetylenedicar-
boxylates and malononitrile catalyzed by 1-methyl-
imidazole.6
The development of novel reactions and useful reagents
which enable the formation of carbon–carbon bonds, and
particularly the construction of ring systems, is a key part
of contemporary organic synthesis.
Polysubstituted benzenes are very useful compounds in
organic chemistry, natural product chemistry, analytical
chemistry and materials science. The regioselective prep-
aration of these compounds is a challenging problem in
organic synthesis.1 Classical methods for the synthesis of
substituted aromatics are based on aromatic substitution
reactions which introduce a substituent to an existing are-
ne. The most common procedures based on this approach
involve electrophilic2 or nucleophilic3 substitution, cata-
lyzed coupling reactions4 and metalation–functionaliza-
tion reactions.5 However, these methods frequently suffer
from disadvantages including multi-step reaction se-
quences, low yields, and serious regiochemical ambiguity
originating from the activating, deactivating and directing
effects of the substituents. On the other hand, modern ap-
proaches entail the regioselective construction of the aro-
matic skeleton starting from acyclic precursors in which
the substitution pattern of the final product is dictated by
the structures and functional groups of the precursors.6
Due to the interesting chemistry of 2,6-dicyanoanilines
the development of synthetic methods which enable easy
access to these useful compounds is desirable. As part of
our studies on the development of efficient and straight-
forward methods for the preparation of organic com-
pounds from readily available building blocks,19 we report
herein a simple synthesis of 3-aryl-2,6-dicyano-5-methyl-
anilines. Thus, a mixture of nitrostyrenes 1a–l and an ex-
cess of malononitrile, in the presence of sodium carbonate
in 80% ethanol, underwent a novel reaction at room tem-
perature to afford the corresponding 3-aryl-2,6-dicyano-
5-methylanilines 2a–l in good yields (Scheme 1, Table 1).
NH2
CN
Me
NC
Ar
NO2
Na2CO3
+
CH2(CN)2
80% EtOH, r.t.
Ar
1
2
Multi-functionalized benzenes possessing electron-donor
and/or acceptor substituents such as 2,6-dicyanoanilines
are of considerable interest. They are key constituents of
a large number of bioactive natural and synthetic com-
pounds,7 and are useful as versatile precursors for asym-
metric syntheses,8 and as important substrates for
nonlinear optical materials9 and molecular electronic de-
vices.10
Scheme 1 Synthesis of 3-aryl-2,6-dicyano-5-methylanilines 2a–l
The products 2a–l were characterized on the basis of IR,
1H and 13C NMR spectroscopy, mass spectrometry and el-
emental analysis. The mass spectrum of 2b displayed the
molecular ion peak at m/z 247, which was consistent with
the structure of the adduct. The IR spectrum showed ab-
sorptions at 3469, 3361, 3232 and 2212 cm–1 indicating
the presence of primary amine and nitrile functional
1
SYNTHESIS 2010, No. 9, pp 1526–1530
x
x
.
x
x
.2
0
1
0
groups. The H NMR spectrum of 2b exhibited three
Advanced online publication: 26.03.2010
DOI: 10.1055/s-0029-1218717; Art ID: T20009SS
© Georg Thieme Verlag Stuttgart · New York
sharp singlets due to two methyl groups (d = 2.42 and d =
2.53) and an aromatic hydrogen (d = 6.70). A fairly broad

PAPER
Synthesis of 3-Aryl-2,6-dicyano-5-methylanilines
1527
signal (d = 5.24) for the amine group and two doublets undergo successive addition of two further molecules of
(d = 7.29 and 7.43, J = 8.0 Hz) for the para-substituted malononitrile to the nitrile triple bonds to form the 1:4 ad-
aryl group were observed. In the 13C NMR spectrum of duct 7 by way of imine 6. Elimination of nitromethane fol-
2b, the two methyl groups resonated at d = 21.3 and 21.4, lowed by a proton shift would yield 1-azatriene
and the signals for the two nitrile carbons were evident at intermediate 8. Intramolecular nucleophilic attack of the
d = 93.8 and 96.2. In addition, three methines and seven methylene nitrile anion on the imine moiety would pro-
quaternary carbons, all in the aromatic region, were in duce highly substituted cyclohexadiene intermediate 9.
agreement with the proposed structure.
Three successive 4-exo-dig cyclizations via nucleophilic
addition of the amine group to the adjacent nitriles and
subsequent ring-opening of the spirocyclic intermediates
may form bicyclic 14 by way of intermediates 10–13. This
may undergo ring-opening and elimination of a molecule
of tricyanoamine to afford 3-aryl-2,6-dicyano-5-methyla-
niline 2. A fairly similar reaction pathway has been pro-
posed for the reaction between ynones and malononitrile
affording the corresponding 2,6-dicyanoanilines.14
Table 1 Synthesis of 3-Aryl-2,6-dicyano-5-methylanilines 2a–l
Product Ar
Mp °C (Lit.)
Yield
(%)a
2a
2b
2c
2d
2e
2f
Ph
191 (188–190)18
222 (220)20
196 (190)20
275 (dec.)
85
77
82
84
83
75
80
71
86
89
79
88
4-MeC6H4
4-MeOC6H4
2-naphthyl
4-FC6H4
When the reaction was performed using a nitrostyrene
prepared from nitroethane instead of nitromethane, the
same 3-aryl-2,6-dicyano-5-methylaniline was obtained,
but in lower yield, indicating that the nitroalkane moiety
is eliminated during the reaction. Thus the methyl group
on the aromatic ring does not originate from the nitrosty-
rene component.
242–244 (241–243)17b
201
3-MeOC6H4
3-ClC6H4
3,4-(MeO)2C6H3
4-ClC6H4
3-MeC6H4
3-FC6H4
2g
2h
2i
240
226 (224–225)17b
238 (236–240)17b
130
In summary, we have developed a novel and simple meth-
od for the synthesis of potentially interesting 3-aryl-2,6-
dicyano-5-methylanilines. Good yields of the products,
relatively short reaction times, a straightforward purifica-
tion process, the use of cheap, readily available starting
materials and mild reaction conditions are the main ad-
vantages of this method. The synthesis of such unsymmet-
ric, highly substituted benzene derivatives has not been
achieved by transition-metal-catalyzed reactions.
2j
2k
203–204
2l
4-BrC6H4
260 (250–252)17b
a Yield of isolated product.
Single-crystal X-ray analysis of nitrile 2a confirmed un-
ambiguously the structures of the products. An ORTEP
diagram of 2a is shown in Figure 1.21
All chemicals were obtained from Merck (Germany), and were used
without further purification. Melting points were measured on an
Electrothermal 9100 apparatus and are uncorrected. IR spectra were
obtained using a Shimadzu IR-460 spectrometer. 1H and 13C NMR
spectra were recorded on Bruker DRX-500 Avance (at 500.1 MHz
and 125.8 MHz) and Bruker DPX-250 (at 250.1 MHz and 62.9
MHz) spectrometers using CDCl3 or DMSO-d6 as the solvent and
TMS as the internal standard. Mass spectra were recorded on an
Agilent Technologies (HP) 5973 mass spectrometer operating at an
ionization potential of 20 eV. Elemental analyses for C, H, and N
were performed using a Heraeus CHN-O-Rapid analyzer.
3-Aryl-2,6-dicyano-5-methylanilines 2; General procedure
A mixture of the appropriate nitrostyrene (1 mmol), malononitrile
(297 mg, 4.5 mmol) and Na2CO3 (3 mmol) in 80% EtOH (4 mL)
was stirred at r.t. for 4 h. The progress of the reaction was monitored
by TLC. After completion of the reaction the resulting white precip-
itate was removed by filtration and washed with H2O (2 × 5 mL) and
then with cold 96% EtOH (2 × 5 mL). The crude product was puri-
fied by recrystallization from EtOAc.
Figure 1 ORTEP representation of the molecular structure of 2a
The formation of the 3-aryl-2,6-dicyano-5-methylaniline
scaffold probably involves a complex multi-step sequence
of reactions. A possible mechanism is proposed in
Scheme 2. The first step may involve Michael addition of
malononitrile to the nitrostyrene 1 in the presence of the
base with formation of 1:1 adduct 3, which may undergo
elimination of hydrogen cyanide to form a,b-unsaturated
nitrile 4. Michael addition of a second molecule of mal-
ononitrile to intermediate 4 leads to adduct 5, which may
2,6-Dicyano-5-methyl-3-phenylaniline (2a)
Yield: 0.198 g (85%); colorless crystals.
IR (KBr): 3469, 3346 and 3236 (NH), 2225 (CN), 1643, 1583,
1469, 1286, 858, 771, 696 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 2.43 (s, 3 H, CH3), 6.66 (br
s, 2 H, NH2), 6.72 (s, 1 H, CH), 7.49–7.51 (m, 5 H, 5 × CH).
Synthesis 2010, No. 9, 1526–1530 © Thieme Stuttgart · New York

1528
M. Adib et al.
PAPER
CN
NO2
Na2CO3
– HCN
CH2(CN)2
Na2CO3
NC
NO2
NC
NO2
CH2(CN)2
+
Ar
Ar
Ar
1
3
4
NC
NC
N
NO2
NH
CN
NC
NC
O2N
NC
–CH(CN)2
–CH(CN)2
– MeNO2
H shift
CN
O2N
Ar
Ar
N
H
Ar
NC
NC
NC
NH
NH
H
5
6
7
NH
NC
NC
N
NC
NC
NC
NC
NC
NC
NH
CN
NH2
NC
Ar
_
NH2
CN
NH
CN
Na2CO3
Ar
Ar
NC
NH2
NH2
8
9
10
NH
CN
CN
CN
N
N
N
NC
NC
N
Me
CN
NH
CN
Ar
CN
CN
Ar
Ar
NC
_
NH2
NC
NH2
NC
NH2
11
12
13
CN
N
+
CN
N
Me
Me
– N(CN)3
Ar
CN
Ar
CN
NH2
NC
NH2
NC
14
2
Scheme 2 A possible mechanism for the formation of products 2
13C NMR (125.8 MHz, DMSO-d6): d = 20.8 (CH3), 92.7 and 95.7 (2
× CN), 115.4 and 116.0 (2 × C), 119.0, 128.3, 128.6 and 129.2 (4 ×
CH), 137.6, 148.1, 149.5 and 153.3 (4 × C).
MS (EI): m/z (%) = 233 (100) [M+], 205 (50), 191 (10), 168 (14),
151 (16), 117 (8), 76 (10).
Anal. Calcd for C16H13N3: C, 77.71; H, 5.30; N, 16.99. Found: C,
77.58; H, 5.37; N, 16.83.
2,6-Dicyano-3-(4-methoxyphenyl)-5-methylaniline (2c)
Yield: 0.216 g (82%); colorless crystals.
IR (KBr): 3465, 3344 and 3244 (NH), 2224 (CN), 1643, 1612,
1582, 1520, 1470, 1443, 1302, 1261, 1186, 1033, 824 cm–1.
1H NMR (500.1 MHz, CDCl3): d = 2.53 (s, 3 H, CH3), 3.87 (s, 3 H,
OCH3), 5.21 (br s, 2 H, NH2), 6.69 (s, 1 H, CH), 7.01 (d, J = 8.6 Hz,
2 H, 2 × CH), 7.49 (d, J = 8.6 Hz, 2 H, 2 × CH).
Anal. Calcd for C15H11N3: C, 77.23; H, 4.75; N, 18.01. Found: C,
77.34; H, 4.81; N, 17.85.
2,6-Dicyano-3-(4-methylphenyl)-5-methylaniline (2b)
Yield: 0.190 g (77%); colorless crystals.
IR (KBr): 3469, 3361 and 3232 (NH), 2212 (CN), 1635, 1587,
1553, 1515, 1442, 1286, 1118, 873, 816 cm–1.
1H NMR (500.1 MHz, CDCl3): d = 2.42 and 2.53 (2 × s, 6 H, 2 ×
CH3), 5.24 (br s, 2 H, NH2), 6.70 (s, 1 H, CH), 7.29 (d, J = 8.0 Hz,
2 H, 2 × CH), 7.43 (d, J = 8.0 Hz, 2 H, 2 × CH).
13C NMR (125.8 MHz, CDCl3): d = 21.4 (CH3), 55.4 (OCH3), 93.7
and 96.1 (2 × CN), 114.3 (CH), 115.4 and 116.3 (2 × C), 120.2 and
129.7 (2 × CH), 129.8, 147.5, 149.7, 152.6 and 160.8 (5 × C).
MS (EI): m/z (%) = 263 (100) [M+], 248 (16), 220 (23), 193 (24),
166 (10), 132 (8).
13C NMR (125.8 MHz, CDCl3): d = 21.3 and 21.4 (2 × CH3), 93.8
and 96.2 (2 × CN), 115.4 and 116.1 (2 × C), 120.2, 128.2 and 129.6
(3 × CH), 134.6, 139.7, 147.6, 150.0 and 152.6 (5 × C).
MS (EI): m/z (%) = 247 (100) [M+], 232 (25), 219 (20), 205 (20),
182 (5), 177 (8), 149 (7), 91 (4).
Anal. Calcd for C16H13N3O: C, 72.99; H, 4.98; N, 15.96. Found: C,
72.77; H, 5.12; N, 15.90.
2,6-Dicyano-5-methyl-3-(2-naphthyl)aniline (2d)
Yield: 0.238 g (84%); colorless crystals.
IR (KBr): 3470, 3357 and 3238 (NH), 2222 (CN), 1639, 1607,
1584, 1470, 1279 cm–1.
Synthesis 2010, No. 9, 1526–1530 © Thieme Stuttgart · New York

PAPER
Synthesis of 3-Aryl-2,6-dicyano-5-methylanilines
1529
1H NMR (500.1 MHz, DMSO-d6): d = 2.47 (s, 3 H, CH3), 6.70 (br
s, 2 H, NH2), 6.87 (s, 1 H, CH), 7.59–7.61 (m, 2 H, 2 × CH), 7.65
(dd, J = 8.7 Hz, 2.2 Hz, 1 H, CH), 7.99–8.02 (m, 2 H, 2 × CH), 8.05
(d, J = 8.9 Hz, 1 H, CH), 8.11 (s, 1 H, CH).
13C NMR (125.8 MHz, DMSO-d6): d = 20.9 (CH3), 92.9 and 95.7 (2
× CN), 115.4 and 116.1 (2 × C), 119.3, 125.8, 126.7, 127.0, 127.6,
127.8, 128.1 and 128.3 (8 × CH), 132.5, 132.8, 135.0, 148.1, 149.5
and 153.4 (6 × C).
2,6-Dicyano-3-(3,4-dimethoxyphenyl)-5-methylaniline (2h)
Yield: 0.208 g (71%); colorless crystals.
IR (KBr): 3485 and 3379 (NH), 2235 (CN), 1632, 1583, 1524,
1479, 1407, 1267, 1230, 1148, 1045, 847, 800 cm–1.
1H NMR (250.1 MHz, DMSO-d6): d = 2.44 (s, 3 H, CH3), 3.81 and
3.82 (2 × s, 6 H, 2 × OCH3), 6.64 (br s, 2 H, NH2), 6.78 (s, 1 H, CH),
7.10–7.11 (m, 2 H, 2 × CH), 7.14 (s, 1 H, CH).
13C NMR (62.9 MHz, DMSO-d6): d = 20.8 (CH3), 55.5 and 55.6 (2
× OCH3), 92.4 and 95.0 (2 × CN), 111.5 and 112.0 (2 × CH), 115.5
and 116.3 (2 × C), 118.8 and 121.0 (2 × CH), 129.7, 147.8, 148.4,
149.3, 149.6 and 153.4 (6 × C).
MS (EI): m/z (%) = 283 (100) [M+], 267 (35), 255 (22), 167 (20),
149 (50), 141 (29), 127 (8).
Anal. Calcd for C19H13N3: C, 80.54; H, 4.62; N, 14.83. Found: C,
80.42; H, 4.81; N, 14.58.
MS (EI): m/z (%) = 293 (100) [M+], 278 (20), 250 (59), 207 (26),
151 (32), 69 (33), 57 (34).
2,6-Dicyano-3-(4-fluorophenyl)-5-methylaniline (2e)
Anal. Calcd for C17H15N3O2: C, 69.61; H, 5.15; N, 14.33. Found: C,
69.60; H, 5.19; N, 14.17.
Yield: 0.209 g (83%); pale yellow crystals.
IR (KBr): 3473, 3354 and 3236 (NH), 2224 (CN), 1641, 1610,
1583, 1562, 1518, 1473, 1446, 1256, 1252, 1167, 833 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 2.43 (s, 3 H, CH3), 6.67 (br
s, 2 H, NH2), 6.73 (s, 1 H, CH), 7.35 (dd, 3JFH = 8.8 Hz, 3JHH = 8.8
Hz, 2 H, 2 × CH), 7.59 (dd, 3JHH = 8.8 Hz, 4JFH = 5.5 Hz, 2 H, 2 ×
CH).
3-(4-Chlorophenyl)-2,6-dicyano-5-methylaniline (2i)
Yield: 0.230 g (86%); colorless crystals.
IR (KBr): 3465, 3352 and 3244 (NH), 2212 (CN), 1645, 1578,
1553, 1497, 1470, 1445, 1379, 1286, 1090, 1012, 822 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 2.43 (s, 3 H, CH3), 6.71 (br
s, 2 H, NH2), 6.73 (s, 1 H, CH), 7.54 (d, J = 8.5 Hz, 2 H, 2 × CH),
7.57 (d, J = 8.5 Hz, 2 H, 2 × CH).
13C NMR (125.8 MHz, DMSO-d6): d = 20.9 (CH3), 92.6 and 96.0 (2
× CN), 115.3 and 115.9 (2 × C), 118.9, 128.6 and 130.2 (3 × CH),
134.2, 136.4, 148.2, 148.3 and 153.3 (5 × C).
MS (EI): m/z (%) = 269 (24) [M+, 37Cl], 267 (100) [M+, 35Cl], 252
(3), 239 (15), 232 (19), 217 (15), 205 (38), 177 (18), 149 (20), 102
(8), 75 (9).
13C NMR (125.8 MHz, DMSO-d6): d = 20.8 (CH3), 92.7 and 95.8 (2
× CN), 115.3 (C), 115.5 (d, 2JFC = 21.8 Hz, CH), 115.9 (C), 119.0
3
4
(CH), 130.6 (d, JFC = 8.6 Hz, CH), 133.9 (d, JFC = 2.4 Hz, C),
148.1, 148.4 and 153.3 (3 × C), 162.6 (d, 1JFC = 246.8 Hz, C–F).
MS (EI): m/z (%) = 251 (100) [M+], 236 (8), 223 (30), 186 (10), 167
(13), 158 (6), 149 (40), 109 (9).
Anal. Calcd for C15H10FN3: C, 71.70; H, 4.01; N, 16.72. Found: C,
71.79; H, 3.89; N, 16.66.
Anal. Calcd for C15H10ClN3: C, 67.30; H, 3.76; N, 15.70. Found: C,
67.44; H, 3.67; N, 15.55.
2,6-Dicyano-3-(3-methoxyphenyl)-5-methylaniline (2f)
Yield: 0.197 g (75%); colorless crystals.
IR (KBr): 3472, 3356 and 3238 (NH), 2222 (CN), 1641, 1602,
1587, 1474, 1417, 1261, 1234, 1165, 1042, 862, 787, 704 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 2.43 (s, 3 H, CH3), 3.80 (s, 3
H, OCH3), 6.64 (br s, 2 H, NH2), 6.75 (s, 1 H, CH), 7.04–7.09 (m, 3
H, 3 × CH), 7.41 (t, J = 7.8 Hz, 1 H, CH).
13C NMR (125.8 MHz, DMSO-d6): d = 20.8 (CH3), 55.2 (OCH3),
92.7 and 95.7 (2 × CN), 113.8 and 114.8 (2 × CH), 115.3 and 116.0
(2 × C), 119.0, 120.5 and 129.7 (3 × CH), 138.9, 148.0, 149.3, 153.3
and 159.1 (5 × C).
2,6-Dicyano-5-methyl-3-(3-methylphenyl)aniline (2j)
Yield: 0.220 g (89%); colorless crystals.
IR (KBr): 3424, 3352 and 3238 (NH), 2214 (CN), 1637, 1587,
1558, 1445, 1288, 1030, 864, 775, 702 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 2.36 and 2.43 (2 × s, 6 H, 2
× CH3), 6.63 (br s, 2 H, NH2), 6.72 (s, 1 H, CH), 7.29 (d, J = 7.7 Hz,
1 H, CH), 7.31 (d, J = 8.1 Hz, 1 H, CH), 7.32 (s, 1 H, CH), 7.38 (t,
J = 7.5 Hz, 1 H, CH).
13C NMR (125.8 MHz, DMSO-d6): d = 20.8 and 20.9 (2 × CH3),
92.7 and 95.6 (2 × CN), 115.4 and 116.1 (2 × C), 119.0, 125.4,
128.5, 128.8 and 129.8 (5 × CH), 137.6, 137.9, 148.0, 149.7 and
153.4 (5 × C).
MS (EI): m/z (%) = 263 (100) [M+], 248 (26), 234 (68), 220 (23),
205 (29), 193 (36), 178 (15), 166 (25), 140 (23), 132 (27).
Anal. Calcd for C16H13N3O: C, 72.99; H, 4.98; N, 15.96. Found: C,
72.81; H, 5.04; N, 15.83.
MS (EI): m/z (%) = 247 (100) [M+], 232 (25), 219 (22), 205 (21),
190 (4), 177 (5), 165 (4), 123 (5), 109 (5), 96 (6).
3-(3-Chlorophenyl)-2,6-dicyano-5-methylaniline (2g)
Yield: 0.214 g (80%); colorless crystals.
Anal. Calcd for C16H13N3: C, 77.71; H, 5.30; N, 16.99. Found: C,
77.65; H, 5.43; N, 16.86.
IR (KBr): 3464, 3356 and 3240 (NH), 2232 (CN), 1645, 1585,
1545, 1404, 1290, 1244, 1095, 854, 800, 710 cm–1.
1H NMR (250.1 MHz, DMSO-d6): d = 2.45 (s, 3 H, CH3), 6.77 (br
s, 2 H, NH2), 6.79 (s, 1 H, CH), 7.48–7.61 (m, 4 H, 4 × CH).
13C NMR (62.9 MHz, DMSO-d6): d = 20.8 (CH3), 92.6 and 96.1 (2
× CN), 115.3 and 115.8 (2 × C), 118.9, 127.1, 128.1, 129.0 and
130.4 (5 × CH), 133.2, 139.5, 147.8, 148.3 and 153.3 (5 × C).
MS (EI): m/z (%) = 269 (31) [M+, 37Cl], 267 (100) [M+, 35Cl], 239
(17), 232 (22), 217 (17), 205 (36), 177 (21), 151 (16), 102 (17), 89
(17), 75 (22).
2,6-Dicyano-3-(3-fluorophenyl)-5-methylaniline (2k)
Yield: 0.198 g (79%); colorless crystals.
IR (KBr): 3472, 3330 and 3237 (NH), 2224 (CN), 1643, 1614,
1581, 1542, 1469, 1421, 1290, 1249, 1139, 858, 750, 706 cm–1.
1H NMR (250.1 MHz, DMSO-d6): d = 2.45 (s, 3 H, CH3), 6.76 (br
s, 2 H, NH2), 6.78 (s, 1 H, CH), 7.31–7.43 (m, 3 H, 3 × CH), 7.57
(dt, 3JHH = 8.3 Hz, 4JFH = 6.5 Hz, 1 H, CH).
13C NMR (62.9 MHz, DMSO-d6): d = 20.3 (CH3), 92.1 and 95.5 (2
× CN), 114.7 (C), 114.8 (d, 2JFC = 22.7 Hz, CH), 115.3 (C), 115.5
(d, 2JFC = 21.9 Hz, CH), 118.4 (CH), 124.1 (d, 4JFC = 2.8 Hz, CH),
130.1 (d, 3JFC = 8.5 Hz, CH), 139.2 (d, 3JFC = 8.1 Hz, C), 147.4 (d,
Anal. Calcd for C15H10ClN3: C, 67.30; H, 3.76; N, 15.70. Found: C,
67.50; H, 3.82; N, 15.52.
Synthesis 2010, No. 9, 1526–1530 © Thieme Stuttgart · New York

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M. Adib et al.
PAPER
(9) (a) Cardozo, T. M.; Nascimento, M. A. C. J. Mater. Sci.
4JFC = 2.0 Hz, C), 147.8 and 152.7 (2 × C), 161.3 (d, JFC = 244.6
Hz, C–F).
1
2005, 40, 3549. (b) Kanis, D. R.; Ratner, M. A.; Marks, T. J.
Chem. Rev. 1994, 94, 195. (c) Murugan, P.;
MS (EI): m/z (%) = 251 (36) [M+], 206 (67), 155 (91), 125 (19), 75
(20), 43 (100).
Shanmugasundaram, P.; Ramakrishnan, V. T.; Srividya, N.;
Ramamurthy, P. Indian J. Chem., Sect. B: Org. Chem. Incl.
Med. Chem. 1998, 37, 737.
Anal. Calcd for C15H10FN3: C, 71.70; H, 4.01; N, 16.72. Found: C,
71.61; H, 4.19; N, 16.68.
(10) (a) Carroll, R. L.; Gorman, C. B. Angew. Chem. Int. Ed.
2002, 41, 4378. (b) van Mullekom, H. A. M.; Vekemans, J.
A. J. M.; Meijer, E. W. Chem. Eur. J. 1998, 4, 1235.
(c) Bendikov, M.; Wudl, F.; Perepichka, D. F. Chem. Rev.
2004, 104, 4891.
(11) (a) Wang, X. S.; Zhang, M. M.; Li, Q.; Yao, C. S.; Tu, S. J.
Tetrahedron 2007, 63, 5265. (b) Sepiol, J.; Milart, P.
Tetrahedron 1985, 41, 5261. (c) Griffiths, J.; Lockwood,
M.; Roozpeikar, B. J. Chem. Soc., Perkin Trans. 2 1977,
1608.
(12) Victory, P.; Borrel, J. I.; Vidal-Ferran, A.; Seoane, C.; Soto,
J. L. Tetrahedron Lett. 1991, 32, 5375.
(13) Xue, D.; Li, J.; Zhang, Z. T.; Deng, J. G. J. Org. Chem. 2007,
72, 5443.
(14) Yi, C.; Blum, C.; Liu, S. X.; Frei, G.; Neels, A.; Renaud, P.;
Leutwyler, S.; Decurtins, S. J. Org. Chem. 2008, 73, 3596.
(15) Khaidem, I. S.; Singh, S. L.; Singh, L. R.; Khan, M. Z. R.
Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.
1996, 35, 911.
3-(4-Bromophenyl)-2,6-dicyano-5-methylaniline (2l)
Yield: 0.275 g (88%); colorless crystals.
IR (KBr): 3450, 3358 and 3244 (NH), 2212 (CN), 1645, 1556,
1501, 1497, 1470, 1445, 1394, 1290, 1080, 1012, 820 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 2.42 (s, 3 H, CH3), 6.72 (br
s, 3 H, CH and NH2), 7.47 (d, J = 8.0 Hz, 2 H, 2 × CH), 7.70 (d,
J = 8.0 Hz, 2 H, 2 × CH).
13C NMR (125.8 MHz, DMSO-d6): d = 20.9 (CH3), 92.5 and 96.0 (2
× CN), 115.4 and 115.9 (2 × C), 118.8 (CH), 122.9 (C), 130.5 and
131.6 (2 × CH), 136.8, 148.2, 148.3 and 153.4 (4 × C).
MS (EI): m/z (%) = 313 (100) [M+, 81Br], 311 (87) [M+, 79Br], 232
(21), 217 (21), 205 (40), 177 (16), 151 (13), 116 (13), 102 (11), 89
(11), 75 (12).
Anal. Calcd for C15H10BrN3: C, 57.71; H, 3.23; N, 13.46. Found: C,
57.81; H, 3.36; N, 13.30.
(16) Singh, F. V.; Kumar, V.; Kumar, B.; Goel, A. Tetrahedron
2007, 63, 10971.
(17) (a) Rong, L.; Han, H.; Yang, F.; Yao, H.; Jiang, H.; Tu, S.
Synth. Commun. 2007, 37, 3767. (b) Rong, L.; Han, H.;
Jiang, H.; Shi, D.; Tu, S. Synth. Commun. 2008, 38, 1044.
(18) Cui, S. L.; Lin, X. F.; Wang, Y. G. J. Org. Chem. 2005, 70,
2866.
Acknowledgment
This research project (6102036/1/02) was supported by the
Research Council of the University of Tehran.
References
(19) (a) Adib, M.; Sheibani, E.; Bijanzadeh, H. R.; Zhu, L. G.
Tetrahedron 2008, 64, 10681. (b) Adib, M.; Sayahi, M. H.;
Mahernia, S.; Zhu, L. G. Tetrahedron Lett. 2008, 49, 945.
(c) Adib, M.; Mohammadi, B.; Bijanzadeh, H. R. Synlett
2008, 3180. (d) Adib, M.; Mohammadi, B.; Bijanzadeh, H.
R. Synlett 2008, 177. (e) Adib, M.; Sayahi, M. H.; Ziyadi,
H.; Bijanzadeh, H. R.; Zhu, L. G. Tetrahedron 2007, 63,
11135. (f) Adib, M.; Sheibani, E.; Mostofi, M.; Ghanbary,
K.; Bijanzadeh, H. R. Tetrahedron 2006, 62, 3435.
(20) Raghukumar, V.; Murugan, P.; Ramakrishnan, T. R. Synth.
Commun. 2001, 31, 3497.
(21) Selected X-ray crystallographic data for compound 2a:
C15H11N3, monoclinic, space group = P21/c, a = 3.9096(5)
Å, b = 21.267(3) Å, c = 14.7077(19) Å, b = 95.388(2)°,
V = 1217.50(4) Å3, T = 295(2) K, Z = 4, Dcalcd = 1.27 g⋅cm–3,
m (Mo-Ka) = 0.078 mm–1, 1579 observed reflections, final
R1 = 0.058, wR2 = 0.150 and for all data R1 = 0.085,
wR2 = 0.163. Crystallographic data for compound 2a have
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC
734566. Copies of these data can be obtained free of charge
from the CCDC via www.ccdc.cam.ac.uk/data_request/cif.
(1) (a) Modern Arene Chemistry; Astruc, D., Ed.; Wiley-VCH:
Weinheim, 2002. (b) Xi, C.; Chen, C.; Lin, J.; Hong, X. Org.
Lett. 2005, 7, 347.
(2) Taylor, R. Electrophilic Aromatic Substitution; Wiley: New
York, 1990.
(3) Zoltewicz, J. A. Top. Curr. Chem. 1975, 59, 33.
(4) Dyker, G. Angew. Chem. Int. Ed. 1999, 38, 1698.
(5) Lin, W. W.; Baron, O.; Knochel, P. Org. Lett. 2006, 8, 5673;
and references cited therein.
(6) Adib, M.; Mohammadi, B.; Mahdavi, M.; Abbasi, A.;
Riazati Kesheh, M. Synlett 2007, 2497; and references cited
therein.
(7) (a) Functional Organic Materials, Synthesis, Strategies and
Applications; Müller, T. J. J.; Bunz, U. H. F., Eds.; Wiley-
VCH: Weinheim, 2007. (b) Thomson, R. H. The Chemistry
of Natural Products; Blackie: Glasgow, 1985. (c) Singh, F.
V.; Vatsyayan, R.; Roy, U.; Goel, A. Bioorg. Med. Chem.
Lett. 2006, 16, 2734.
(8) (a) Maitraie, D.; Reddy, G. V.; Rao, V. V. V. N. S. R.;
Ravikanth, S.; Narsaiah, B.; Rao, P. S.; Ravikumar, K.;
Sridhar, B. Tetrahedron 2005, 61, 3999. (b) Andersen, N.
G.; Maddaford, S. P.; Keay, B. A. J. Org. Chem. 1996, 61,
9556.
Synthesis 2010, No. 9, 1526–1530 © Thieme Stuttgart · New York