A green method for the synthesis of thiochromene derivatives in ionic liquids

Article abstract of DOI:10.1002/jhet.688

Controlling the pH value by changing the negative ion of ionic liquids, the same reactions of aromatic aldehyde, 2-(2,3-dihydrothiochromen-4-ylidene) malononitrile and malononitrile product unaromatized and aromatized 6H-benzo[c]thiochromene derivatives in high yields. The nice features of these procedures include mild reactions condition, simple operations, high yields, and environmentally benign.

Full text of DOI:10.1002/jhet.688

1056
A Green Method for the Synthesis of Thiochromene
Derivatives in Ionic Liquids
Vol 48
Xiang-Shan Wang,* Jian-Rong Wu, Jie Zhou, and Mei-Mei Zhang
School of Chemistry and Chemical Engineering, The Key Laboratory of Biotechnology on Medical
Plant, Xuzhou Normal University, Xuzhou, Jiangsu 221116, People’s Republic of China
*E-mail: xswang1974@yahoo.com
Received May 25, 2010
DOI 10.1002/jhet.688
Published online 13 May 2011 in Wiley Online Library (wileyonlinelibrary.com).
Controlling the pH value by changing the negative ion of ionic liquids, the same reactions of aro-
matic aldehyde, 2-(2,3-dihydrothiochromen-4-ylidene) malononitrile and malononitrile product unarom-
atized and aromatized 6H-benzo[c]thiochromene derivatives in high yields. The nice features of these
procedures include mild reactions condition, simple operations, high yields, and environmentally
benign.
J. Heterocyclic Chem., 48, 1056 (2011).
INTRODUCTION
not only as a green media but also as facile recycle cat-
alysts for many organic reactions [6].
Control of selectivity, for example, chemo-, stereo-,
and region-selectivity, is among the most important
objectives in organic chemistry. Many different process
parameters such as temperature, pressure, solvent, as
well as catalyst type, and other factors can be utilized to
modulate the selectivity of synthetic transformations [1].
Multi-component reactions (MCRs) play an important
role in modern synthetic organic chemistry since they
generally occur in a single pot and exhibit a high atom-
economy and selectivity. They provide a powerful tool
toward the one-pot synthesis of diverse and complex
compounds [2]. For multi-component reactions involv-
ing the simultaneous molecular interaction of three or
more components, the issue of selectivity is of particular
significance due to the high probability of several poten-
tial parallel reaction pathways leading to different prod-
uct classes [3].
As a continuation of our research devoted to the de-
velopment of new methods for the preparation of het-
erocycles in environmental benign media [7], we
think that the same reaction may give different prod-
ucts, changing the different negative ions in ionic
liquids to control the pH value of the reaction media.
In this article, we would like to report a green
synthesis of 6H-benzo[c]thiochromene-8,8,10(7H)-tri-
carbonitrile and 6H-benzo[c]thiochromene-8,10-dicar-
bonitrile derivatives using the same reactants by
changing the negative anion to control the pH value
in ionic liquids.
RESULTS AND DISCUSSION
Treatment of aromatic aldehyde 1 with malononi-
Ionic liquids have attracted increasing interest in the
context of green synthesis in the past few years. They
have been much more used as solvents for a large num-
ber of organic transformations [4]. In the structure of
the known ionic liquids, the positive ion always bases
on the 1-N-alkyl-3-methyl imidazolium cation. On the
other hand, their negative ions are alterable, such as
Clꢀ, Brꢀ, BF4ꢀ, PF6ꢀ, CF3SO3ꢀ, CF3CO2ꢀ, HSO4ꢀ, OHꢀ,
and CH3CO2ꢀ. According to the literature [5], some of
them are acidic media, such as BF4ꢀ, PF6ꢀ, and HSO4ꢀ,
while many ionic liquids indicate basic property, for
example, Clꢀ, Brꢀ, and OHꢀ. Sometimes, they are used
trile
malononitrile
2
and 2-(2,3-dihydrothiochromen-4-ylidene)
in the acidic ionic liquid of
3
[BMIm]BF4 at room temperature produced the corre-
sponding 9-amino-7-aryl-6H-benzo[c]thiochromene-
8,8,10(7H)-tricarbonitrile 4 in high yields (Scheme
1). As our initial assumption, changing the negative
ions in the ionic liquid from BF4ꢀ to Brꢀ, [BMIm]Br
was selected as a basic ionic liquid to perform the
same reaction. To our delight, the design proceeded
smoothly and provided excellent yields of aromatized
9-amino-7-phenyl-6H-benzo[c]thiochromene-8,10-di-
carbonitrile derivatives 5 at 50ꢁC (Scheme 1).
C
V
2011 HeteroCorporation

September 2011 A Green Method for the Synthesis of Thiochromene Derivatives in Ionic Liquids
1057
Scheme 1. Reaction of 1, 2, and 2-(2,3-dihydrothiochromen-4-ylidene)malononitrile.
In our initial study, using the conversion of 2,4-
dichlorobenzaldehyde malononitrile 2 and 2-(2,3-dihy-
drothiochromen-4-ylidene) malononitrile 3 as a model
reaction, different negative ions in ionic liquids were
selected as solvents to this reaction (Table 1). It was
found that negative ion of BF4ꢀ gives the best result (4a,
98 % yield) in the negative ions, while PF6ꢀ and HSO4ꢀ
gave 86% and 70% yields, respectively. In the basic
ionic liquids, the same reaction giving 83% yield in the
ionic liquid of [BMIm]Br fꢀor 5a is better than those of
Clꢀ (77%, 50ꢁC) and OH (64%, room temperature).
The reaction temperature also played a key in the reac-
tion, the higher temperature is better for the elimination
reaction. In our control reactions, it was found that the
appropriate temperature for the aromatized product 5a is
50ꢁC, while room temperature is suitable for the forma-
tion of product 4a.
These alterable conditions were applied for the con-
version of various kinds of aromatic aldehydes into the
corresponding benzo[c]thiochromene analogues (Table
2, entries 1–18). Among these analogues, the yields of 4
or 5 were not sensitive to the electronic properties of
the aromatic ring in the presence of electron-withdraw-
ing groups (such as halide and nitro) or electron-donat-
ing groups (such as alkoxyl group). They all gave the
desired 6H-benzo[c]thiochromene-8,8,10(7H)-tricarboni-
trile 4 in the acidic ionic liquid of [BMIm]BF4 (Table 2,
entries 1–7), while in the basic one of [BMIm]Br
yielded aromatized 6H-benzo[c]thiochromene-8,10-
dicarbonitrile derivatives (Table 2, entries 8–18). All the
compounds were characterized by 1H NMR, IR, and
HRMS.
According to the literature [8], although the detailed
mechanism of the above reaction has not been clarified,
the formation of benzo[c]thiochromene derivatives 4
and 5 can be tentatively explained by the pathway pre-
sented in Scheme 2. The product of Knoevenagel con-
densation I may be formed first from aromatic aldehyde
and malononitrile. In the following step, the Michael
addition reaction between 3 and I takes place to produce
intermediate II, followed by intra-molecular cyclization
to form III. III isomerizes to give the final product 4 in
the acidic ionic liquid. While in the basic ionic liquid of
[BMIm]Br, the solvent helps to lose cyanide ion (CNꢀ)
to give aromatized 6H-benzo[c]thiochromene-8,10-dicar-
bonitrile derivatives 5.
In our continued study, the 4a can be converted to 5a
in the basic ionic liquid of [BMIm]Br at 50ꢁC in 72%
Table 2
Synthetic results of 4 and 5 in ionic liquids.a
Entry
Ar
Products Time (h) yields (%)b
1
2
3
2,4-Cl2C6H3
3,5-(CH3O)2C6H3
3,4-(CH3O)2C6H3
2,3-(CH3O)2C6H3
2,3-Cl2C6H3
3-ClC6H4
4a
4b
4c
4d
4e
4f
4g
5a
5b
5c
5d
5e
5f
10
13
6
98
88
89
93
93
92
87
83
87
93
95
87
96
95
90
93
87
84
Table 1
Synthesis of 4a and 5a at different reaction conditions.a
4
5
8
Yieldsb
(%)
10
12
12
8
Entry
T (ꢁC)
Solvents
Product
6
7
8
2-ClC6H4
c
1
2
3
4
5
6
7
8
Room temperature [BMIm]BF4
Room temperature [BMIm]PF6
Room temperature [BMIm]HSO4
4a
4a
4a
5a
5a
5a
5a
5a
98
86
70
83
77
64
2,4-Cl2C6H3
3,4-(CH3O)2C6H3
4-FC6H4
9
7
10
11
12
13
14
15
16
17
18
10
10
8
50
50
[BMIm]Brc
[BMIm]Cl
2-FC6H4
4-BrC6H4
Room temperature [BMIm]OH
Room temperature [BMIm]Br
2-BrC6H4
4-ClC6H4
3,5-(CH3O)2C6H3
2,3-Cl2C6H3
3-ClC6H4
8
Trace
83
5g
5h
5i
5j
5k
6
9
80
[BMIm]Br
8
7
10
a Reaction condition: 1 (1 mmol) and 2 (0.073 g, 1.1 mmol), and 2-
(2,3-dihydrothiochromen-4-ylidene)malononitrile (0.212 g, 1 mmol), 2
mL ionic liquid.
2-ClC6H4
b Isolated yields.
a Reaction condition: 1 (1 mmol) and 2 (0.073 g, 1.1 mmol), and 2-
(2,3-dihydrothiochromen-4-ylidene)malononitrile (0.212 g, 1 mmol), 2
mL [BMIm][BF4], Room temperature, or [BMIm]Br, 50ꢁC.
b Isolated yields.
c The pH value of [BMIm]BF4 prepared in our lab is about 5.84, while
[BMIm]Br shows weak alkaline with slightly higher pH value (7.28).
These data are determined on Model PHS-3C pH meter.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1058
X.-S. Wang, J.-R. Wu, J. Zhou, and M.-M. Zhang
Vol 48
Scheme 2. Possible mechanism for the formation of products 4 and 5.
1593, 1467, 1432, 1411, 1388, 1347, 1318, 1292, 1258, 1206,
1160, 1098, 1068, 1053, 928, 853, 771; 1H NMR (400 MHz,
DMSO-d6, d, ppm): 3.09 (d, J ¼ 16.4 Hz, 1H, CH2), 3.57 (d,
J ¼ 16.0 Hz, 1H, CH2), 3.74 (s, 6H, 2CH3O), 4.83 (s, 1H,
CH), 6.59 (s, 1H, ArH), 6.64 (s, 2H, ArH), 7.28–7.31 (m, 2H,
ArH), 7.40 (t, J ¼ 7.2 Hz, 1H, ArH), 7.50 (d, J ¼ 7.2 Hz, 1H,
ArH), 7.75 (s, 2H, NH2).
9-Amino-7-(3,4-dimethoxyphenyl)-6H-benzo[c]thiochromene-
8,8,10(7H)-tricarbonitrile (4c). m.p. 218–220ꢁC; IR (KBr, m,
cmꢀ1): 3443, 3342, 3237, 2957, 2939, 2912, 2200, 1633,
1607, 1572, 1518, 1468, 1448, 1392, 1349, 1276, 1254,
1236, 1216, 1186, 1161, 1140, 1025, 875, 759, 763, 736; 1H
NMR (400 MHz, DMSO-d6, d, ppm): 3.08 (d, J ¼ 16.0 Hz,
1H, CH2), 3.59 (d, J ¼ 16.0 Hz, 1H, CH2), 3.72 (s, 3H,
CH3O), 3.78 (s, 3H, CH3O), 4.84 (s, 1H, CH), 6.99–7.04 (m,
2H, ArH), 7.09 (s, 1H, ArH), 7.26–7.33 (m, 2H, ArH), 7.41
(d, J ¼ 8.0 Hz, 1H, ArH), 7.51 (d, J ¼ 8.0 Hz, 1H, ArH),
7.72 (s, 2H, NH2).
HRMS (ESI, m/z) calcd for C24H18N4O2SNa (M þ Naþ)
449.1048, found 449.1059.
9-Amino-7-(2,3-dimethoxyphenyl)-6H-benzo[c]thiochromene-
8,8,10(7H)-tricarbonitrile (4d). m.p. 249–251ꢁC; IR (KBr, m,
cmꢀ1): 3433, 3328, 3188, 3011, 2970, 2933, 2837, 2202, 1671,
1640, 1584, 1482, 1433, 1390, 1280, 1216, 1166, 1093, 1073,
yield. This result indicates that the product 4a may be
formed in the formation of aromatized product 5a.
Meanwhile, it also demonstrates that the pH value of
the ionic liquid plays a key in the formation of products
4 and 5.
1
1039, 1000, 807, 780, 752, 737; H NMR (400 MHz, CDCl3,
d, ppm): 2.88 (d, J ¼ 15.6 Hz, 1H, CH2), 3.59 (d, J ¼ 15.6
Hz, 1H, CH2), 3.90 (s, 3H, CH3O), 4.03 (s, 3H, CH3O), 4.87
(s, 1H, CH), 5.53 (s, 2H, NH2), 6.94 (d, J ¼ 8.0 Hz, 1H,
ArH), 7.00 (d, J ¼ 8.0 Hz, 1H, ArH), 7.06 (t, J ¼ 16.0 Hz,
1H, ArH), 7.23–7.29 (m, 2H, ArH), 7.35 (d, J ¼ 8.0 Hz, 1H,
ArH), 7.61 (d, J ¼ 7.2 Hz, 1H, ArH).
EXPERIMENTAL
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a Tensor 27 spec-
1
trometer in KBr pellet. H NMR spectra was obtained from a
solution in DMSO-d6 with Me4Si as internal standard using a
Bruker-400 spectrometer. HRMS analyses were carried out
using a Bruker-micro-TOF-Q-MS analyzer.
HRMS (ESI, m/z) calcd for C24H18N4O2SNa (M þ Naþ)
449.1048, found 449.1058.
9-Amino-7-(2,3-dichlorophenyl)-6H-benzo[c]thiochromene-
8,8,10(7H)-tricarbonitrile (4e). m.p. 160–161ꢁC; IR (KBr, m,
cmꢀ1): 3437, 2929, 2880, 2802, 2210, 1658, 1586, 1509, 1492,
1442, 1419, 1385, 1341, 1255, 1214, 1179, 1097, 1049, 790,
General procedure for the synthesis of 9-amino-7-aryl-
6H-benzo[c]thiochromene-8,8,10(7H)-tricarbonitrile 4. A
dry 50-mL flask was charged with aromatic aldehyde (1.0
mmol), malononitrile (0.073 g, 1.1 mmol), 2-(2,3-dihydrothio-
chromen-4-ylidene)malononitrile (0.212 g, 1 mmol), and ionic
liquid of [BMIm]BF4 (2 mL). The reaction mixture was stirred
at room temperature for 6–12 h, and then a small amount of
water (5 mL) was added to the mixture, and the generated yel-
low solid was filtered off. The water in the filtrate was
removed by distillation under reduced pressure, and the ionic
liquid in the residue could be reusable by being evaporated at
80ꢁC for 4 h at vacuum. The crude yellow products were
washed with water and purified by recrystallization from DMF
and water, then dried at 80ꢁC for 2 h under vacuum to give 4.
9-Amino-7-(2,4-dichlorophenyl)-6H-benzo[c]thiochromene-
8,8,10(7H)-tricarbonitrile (4a). m.p. 138–139ꢁC; IR (KBr, m,
cmꢀ1): 3437, 3195, 3067, 2933, 2895, 2204, 1671, 1640, 1581,
1558, 1508, 1468, 1434, 1411, 1386, 1256, 1214, 1142, 1102,
1052, 850, 813, 762, 733; 1H NMR (400 MHz, DMSO-d6, d,
ppm): 3.01 (d, J ¼ 16.4 Hz, 1H, CH2), 3.61 (d, J ¼ 16.4 Hz,
1H, CH2), 5.09 (s, 1H, CH), 7.31 (t, J ¼ 5.2 Hz, 2H, ArH),
7.41 (d, J ¼ 8.0 Hz, 2H, ArH), 7.55–7.61 (m, 2H, ArH), 7.89
(d, J ¼ 14.4 Hz, 3H, ArH þ NH2).
1
761, 732; H NMR (400 MHz, DMSO-d6, d, ppm): 3.06 (d, J
¼ 16.4 Hz, 1H, CH2), 3.60 (d, J ¼ 16.4 Hz, 1H, CH2), 5.20
(s, 1H, CH), 7.29–7.34 (m, 2H, ArH), 7.41 (d, J ¼ 8.0 Hz,
2H, ArH), 7.50 (t, J ¼ 8.0 Hz, 1H, ArH), 7.56 (d, J ¼ 8.0 Hz,
1H, ArH), 7.79 (d, J ¼ 8.0 Hz, 1H, ArH), 7.88 (s, 2H, NH2).
HRMS (ESI, m/z) calcd for C22H12Cl2N4SNa (M þ Naþ)
457.0057, found 457.0059.
9-Amino-7-(3-chlorophenyl)-6H-benzo[c]thiochromene-8,8,
10(7H)-tricarbonitrile (4f). m.p. 147–149ꢁC; IR (KBr, m,
cmꢀ1): 3338, 3192, 2207, 1665, 1589, 1474, 1430, 1408, 1385,
1
1215, 1099, 783, 770, 739; H NMR (400 MHz, DMSO-d6, d,
ppm): 3.09 (d, J ¼ 16.4 Hz, 1H, CH2), 3.61 (d, J ¼ 16.0 Hz,
1H, CH2), 4.99 (s, 1H, CH), 7.28–7.32 (m, 2H, ArH), 7.42 (d,
J ¼ 8.0 Hz, 2H, ArH), 7.49 (m, 4H, ArH), 7.78 (s, 2H, NH2).
HRMS (ESI, m/z) calcd for C22H13ClN4SNa (M þ Naþ)
423.0047, found 423.0464.
9-Amino-7-(2-chlorophenyl)-6H-benzo[c]thiochromene-8,8,
10(7H)-tricarbonitrile (4g). m.p. 221–223ꢁC; IR (KBr, m,
cmꢀ1): 3428, 3134, 2204, 1665, 1637, 1579, 1494, 1471, 1438,
1413, 1392, 1337, 1254, 1214, 1187, 1101, 1034, 839, 766,
731; 1H NMR (400 MHz, DMSO-d6, d, ppm): 2.99 (d, J ¼
16.4 Hz, 1H, CH2), 3.61 (d, J ¼ 16.0 Hz, 1H, CH2), 5.09 (s,
1H, CH), 7.27–7.34 (m, 2H, ArH), 7.39–7.53 (m, 4H, ArH)
7.56 (d, J ¼ 8.0 Hz, 1H, ArH), 7.66 (d, J ¼ 8.0 Hz, 1H,
ArH), 7.87 (s, 2H, NH2).
9-Amino-7-(3,5-dimethoxyphenyl)-6H-benzo[c]thiochromene-
8,8,10(7H)-tricarbonitrile (4b). m.p. 235–236ꢁC; IR (KBr, m,
cmꢀ1): 3666, 3325, 3197, 3002, 2939, 2874, 2840, 2206, 1643,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2011 A Green Method for the Synthesis of Thiochromene Derivatives in Ionic Liquids
1059
HRMS (ESI, m/z) calcd for C22H14ClN4S (M þ Hþ)
401.0628, found 401.0609.
1160, 1071, 1011, 828, 770, 754; 1H NMR (400 MHz,
DMSO-d6, d, ppm): 3.42 (s, 2H, CH2), 6.77 (s, 2H, NH2),
7.38–7.47 (m, 4H, ArH), 7.57 (d, J ¼ 8.0 Hz, 1H, ArH), 7.77
(d, J ¼ 8.4 Hz, 2H, ArH), 8.12 (d, J ¼ 8.0 Hz, 1H, ArH).
HRMS (ESI, m/z) calcd for C21H12BrN3SNa (M þ Naþ)
439.9833, found 439.9849.
General procedure for the synthesis of 9-amino-7-aryl-6H-
benzo[c]thiochromene-8,10-dicarbonitrile derivatives 5. A
dry 50-mL flask was charged with aromatic aldehyde (1.0
mmol), malononitrile (0.073 g, 1.1 mmol), 2-(2,3-dihydrothio-
chromen-4-ylidene)malononitrile (0.212 g, 1.0 mmol), and ionic
liquid of [BMIm]Br (2 mL). The reaction mixture was stirred at
50ꢁC for 6–10 h and then cooled down to room temperature. A
small amount of water (5 mL) was added to the mixture, and
the generated yellow solid was filtered off. The water in the fil-
trate was removed by distillation under reduced pressure, and the
ionic liquid in the residue could be reusable by being evaporated
at 80ꢁC for 4 h at vacuum. The crude yellow products were
washed with water and purified by recrystallization from DMF
and water, then dried at 80ꢁC for 2 h under vacuum to give 5.
9-Amino-7-(2,4-dichlorophenyl)-6H-benzo[c]thiochromene-
8,10-dicarbonitrile (5a). m.p. 256–257ꢁC; IR (KBr, m, cmꢀ1):
3465, 3353, 3241, 3094, 3059, 2222, 1639, 1588, 1563, 1482,
1425, 1380, 1301, 1262, 1207, 1160, 1100, 1060, 887, 813,
758; 1H NMR (400 MHz, DMSO-d6, d, ppm): 3.27 (d, J ¼
14.8 Hz, 1H, CH2), 3.33 (d, J ¼ 14.8 Hz, 1H, CH2), 6.87 (s,
2H, NH2), 7.42–7.46 (m, 2H, ArH), 7.53 (d, J ¼ 8.4 Hz, 1H,
ArH), 7.58 (d, J ¼ 7.6 Hz, 1H, ArH), 7.67 (d, J ¼ 8.0 Hz,
1H, ArH), 7.91 (s, 1H, ArH), 8.16 (d, J ¼ 7.6 Hz, 1H, ArH).
HRMS (ESI, m/z) calcd for C21H11Cl2N3SNa (M þ Naþ)
429.9948, found 429.9959.
9-Amino-7-(2-bromophenyl)-6H-benzo[c]thiochromene-8,10-
dicarbonitrile (5f). m.p. 263–265ꢁC; IR (KBr, m, cmꢀ1): 3358,
3232, 2913, 2218, 1632, 1555, 1476, 1425, 1296, 1270, 1202,
1149, 1073, 1026, 795, 754; 1H NMR (400 MHz, DMSO-d6,
d, ppm): 3.21 (d, J ¼ 14.4 Hz, 1H, CH2), 3.30 (d, J ¼ 14.4
Hz, 1H, CH2), 6.85 (s, 2H, NH2), 7.40–7.51 (m, 4H, ArH),
7.58 (d, J ¼ 7.6 Hz, 2H, ArH), 7.86 (d, J ¼ 8.0 Hz, 1H,
ArH), 8.16 (d, J ¼ 8.0 Hz, 1H, ArH).
HRMS (ESI, m/z) calcd for C21H12BrN3SNa (M þ Naþ)
439.9833, found 439.9810.
9-Amino-7-(4-chlorophenyl)-6H-benzo[c]thiochromene-8,
10-dicarbonitrile (5g). m.p. 240–242ꢁC; IR (KBr, m, cmꢀ1):
3466, 3349, 3235, 2213, 1634, 1586, 1569, 1553, 1494, 1423,
1395, 1296, 1271, 1206, 1159, 1092, 1015, 954, 908, 831,
771, 755; 1H NMR (400 MHz, DMSO-d6, d, ppm): 3.42 (s,
2H, CH2), 6.78 (s, 2H, NH2), 7.41–7.47 (m, 4H, ArH), 7.57
(d, J ¼ 8.0 Hz, 1H, ArH), 7.63 (d, J ¼ 8.4 Hz, 2H, ArH),
8.12 (d, J ¼ 7.6 Hz, 1H, ArH).
HRMS (ESI, m/z) calcd for C21H13ClN3S (M þ Hþ)
374.0519 found 374.0514.
9-Amino-7-(3,5-dimethoxyphenyl)-6H-benzo[c]thiochromene-
8,10-dicarbonitrile (5h). m.p. 238–239ꢁC; IR (KBr, m, cmꢀ1):
3424, 3345, 3247, 3055, 2940, 2840, 2216, 1646, 1593, 1552,
1450, 1425, 1332, 1291, 1261, 1208, 1162, 1064, 989, 926,
9-Amino-7-(3,4-dimethoxyphenyl)-6H-benzo[c]thiochromene-
8,10-dicarbonitrile (5b). m.p. 267–269ꢁC; IR (KBr, m, cmꢀ1):
3488, 3386, 2997, 2938, 2840, 2212, 1617, 1586, 1571, 1553,
1515, 1470, 1431, 1368, 1320, 1255, 1182, 1140, 1020, 814,
763; 1H NMR (400 MHz, DMSO-d6, d, ppm): 3.46 (d, J ¼
14.4 Hz, 1H, CH2), 3.56 (d, J ¼ 14.8 Hz, 1H, CH2), 3.78 (s,
3H, CH3O), 3.84 (s, 3H, CH3O), 6.67 (s, 2H, NH2), 6.96 (d, J
¼ 8.4 Hz, 1H, ArH), 7.01 (s, 1H, ArH), 7.12 (d, J ¼ 8.4 Hz,
1H, ArH), 7.41–7.46 (m, 2H, ArH), 7.57 (d, J ¼ 8.0 Hz, 1H,
ArH), 8.01 (d, J ¼ 7.6 Hz, 1H, ArH).
1
845, 791, 755; H NMR (400 MHz, DMSO-d6, d, ppm): 3.46
(s, 2H, CH2), 3.79 (s, 6H, 2CH3O), 6.55 (s, 2H, NH2), 6.65 (s,
1H, ArH), 6.71 (s, 2H, ArH), 7.39–7.46 (m, 2H, ArH), 7.57 (d,
J ¼ 7.2 Hz, 1H, ArH), 8.11 (d, J ¼ 7.2 Hz, 1H, ArH).
HRMS (ESI, m/z) calcd for C23H17N3O2SNa (M þ Naþ)
422.0939, found 422.0945.
9-Amino-7-(2,3-dichlorophenyl)-6H-benzo[c]thiochromene-
8,10-dicarbonitrile (5i). m.p. 224–225ꢁC; IR (KBr, m, cmꢀ1):
3465, 3394, 3352, 3239, 2921, 2850, 2211, 1619, 1560, 1471,
1448, 1424, 1362, 1296, 1272, 1190, 1154, 1050, 800, 782,
754; 1H NMR (400 MHz, DMSO-d6, d, ppm): 3.27 (d, J ¼
14.8 Hz, 1H, CH2), 3.33 (d, J ¼ 16.0 Hz, 1H, CH2), 6.89 (s,
2H, NH2), 7.42–7.48 (m, 3H, ArH), 7.57 (d, J ¼ 8.0 Hz, 2H,
ArH), 7.84 (d, J ¼ 8.0 Hz, 1H, ArH), 8.16 (d, J ¼ 8.0 Hz,
1H, ArH).
HRMS (ESI, m/z) calcd for C23H17N3O2SNa (M þ Naþ)
422.0939, found 422.0957.
9-Amino-7-(4-fluorophenyl)-6H-benzo[c]thiochromene-8,10-
dicarbonitrile (5c). m.p. 261–263ꢁC; IR (KBr, m, cmꢀ1): 3478,
3362, 2209, 1621, 1554, 1473, 1424, 1297, 1270, 1215, 1156,
1
1098, 1017, 844, 763, 735; H NMR (400 MHz, DMSO-d6, d,
ppm): 3.42 (s, 2H, CH2), 6.75 (s, 2H, NH2), 7.38–7.45 (m, 4H,
ArH), 7.47–7.51 (m, 2H, ArH), 7.57 (d, J ¼ 7.6 Hz, 1H,
ArH), 8.12 (d, J ¼ 7.6 Hz, 1H, ArH).
HRMS (ESI, m/z) calcd for C21H11Cl2N3SNa (M þ Naþ)
HRMS (ESI, m/z) calcd for C21H12FN3SNa (M þ Naþ)
380.0634, found 380.0654.
429.9948, found 429.9951.
9-Amino-7-(3-chlorophenyl)-6H-benzo[c]thiochromene-8,10-
dicarbonitrile (5j). m.p. 228–229ꢁC; IR (KBr, m, cmꢀ1):
3456, 3349, 3239, 3067, 2213, 1634, 1553, 1479, 1427,
1294, 1272, 1205, 1154, 1094, 1077, 1042, 999, 948, 878,
9-Amino-7-(2-fluorophenyl)-6H-benzo[c]thiochromene-8,10-
dicarbonitrile (5d) m.p. 259–261ꢁC; IR (KBr, m, cmꢀ1): 3461,
3346, 3240, 2223, 1633, 1615, 1556, 1493, 1447, 1426, 1361,
1299, 1259, 1200, 1157, 1101, 1032, 951, 894, 822, 762; 1H
NMR (400 MHz, DMSO-d6, d, ppm): 3.35 (d, J ¼ 14.4 Hz,
1H, CH2), 3.42 (d, J ¼ 14.4 Hz, 1H, CH2), 6.83 (s, 2H, NH2),
7.39–7.50 (m, 5H, ArH), 7.57–7.64 (m, 2H, ArH), 8.15 (d, J
¼ 8.0 Hz, 1H, ArH).
1
800, 754; H NMR (400 MHz, CDCl3, d, ppm): 3.39 (d, J ¼
14.4 Hz, 1H, CH2), 3.44 (d, J ¼ 14.4 Hz, 1H, CH2), 5.35 (s,
2H, NH2), 7.26 (s, 1H, ArH), 7.33 (s, 1H, ArH), 7.37–7.41
(m, 2H, ArH), 7.49–7.53 (m, 3H, ArH), 8.17 (d, J ¼ 6.0 Hz,
1H, ArH).
HRMS (ESI, m/z) calcd for C21H13FN3S (M
358.0814, found 358.0813.
þ
Hþ)
HRMS (ESI, m/z) calcd for C21H12ClN3SNa (M þ Naþ)
396.0338, found 396.0337.
9-Amino-7-(4-bromophenyl)-6H-benzo[c]thiochromene-8,10-
dicarbonitrile (5e). m.p. 253–254ꢁC; IR (KBr, m, cmꢀ1): 3463,
3353, 3234, 2213, 1633, 1553, 1490, 1421, 1391, 1295, 1269,
9-Amino-7-(2-chlorophenyl)-6H-benzo[c]thiochromene-8,10-
dicarbonitrile (5k). m.p. 259–260ꢁC; IR (KBr, m, cmꢀ1): 3463,
3356, 3234, 2919, 2220, 1632, 1554, 1480, 1450, 1427, 1296,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1060
X.-S. Wang, J.-R. Wu, J. Zhou, and M.-M. Zhang
Vol 48
1272, 1203, 1152, 1060, 1031, 756; 1H NMR (400 MHz,
CDCl3, d, ppm): 3.26 (d, J ¼ 14.4 Hz, 1H, CH2), 3.41 (d, J ¼
14.4 Hz, 1H, CH2), 5.33 (s, 2H, NH2), 7.33–7.40 (m, 3H,
ArH), 7.44–7.52 (m, 3H, ArH), 7.57 (d, J ¼ 8.0 Hz, 1H,
ArH), 8.20 (d, J ¼ 5.6 Hz, 1H, ArH).
´
[2] (a) Lieby-Muller, F.; Constantieux, T.; Jean Rodriguez, J. J
Am Chem Soc 2005, 127, 17176; (b) Chebanov, V. A.; Saraev, V. E.;
Desenko, S. M.; Chernenko, V. N.; Knyazeva, I. V.; Groth, U.; Glas-
nov, T. N.; Kappe, C. O. J Org Chem 2008, 73, 5110; (c) Sunderhaus,
J. D.; Dockendorff, C.; Martin, S. F. Org Lett 2007, 9, 4223.
[3] (a) Wang, Z.; Zhou, L.; El-Boubbou, K.; Ye, X.-S.; Huang,
X. J Org Chem 2007, 72, 6409; (b) Heravi, M. M.; Baghernejad, B.;
Oskooie, H. A.; Hekmatshoar, R. Tetrahedron Lett 2008, 49, 6101;
(c) Willy, B.; Mu¨ller, T. J. J. Eur J Org Chem 2008, 4157; (d)
Umkehrer, M.; Kolb, J.; Burdack, C.; Hiller, W. Synlett 2005, 79.
[4] (a) Welton, T. Chem Rev 1999, 99, 2071; (b) Dupont, J.;
de Souza, R. F.; Suarez, P. A. Z. Chem Rev 2002, 102, 3667; (c) Mar-
tins, M. A. P.; Frizzo, C. P.; Moreira, D. N.; Zanatta, N.; Bonacorso,
H. G. Chem Rev 2008, 108, 2015.
HRMS (ESI, m/z) calcd for C21H12ClN3SNa (M þ Naþ)
396.0338, found 396.0337.
CONCLUSIONS
In conclusion, unaromatized and aromatized 6H-ben-
zo[c]thiochromene derivatives were prepared in high
yields by the same reactions of aromatic aldehyde, 2-
[5] (a) Campbell, J. L. E.; Johnson, K. E. J Am Chem Soc
1995, 117, 7791; (b) Gu, Y. L.; Peng, J. J.; Qiao, K.; Yang, H. Z.;
Shi, F.; Deng, Y. Q. Prog Chem 2003, 15, 222.
(2,3-dihydrothiochromen-4-ylidene)malononitrile
and
malononitrile in ionic liquid of [BMIm]BF4, and
[BMIm]Br, respectively. The nice features of these pro-
cedures include mild reactions condition, simple opera-
tions, high yields, and environmentally benign.
[6] (a) Fang, D.; Luo, J.; Zhou, X. L.; Liu, Z. L. Catal Lett
2007, 116, 76; (b) Yavari, I.; Kowsari, E. Synlett 2008, 897; (c) Hajipour,
A. R.; Ghayeb, Y.; Sheikhan, N.; Ruoho, A. E. Tetrahedron Lett 2009, 50,
5649; (d) Huang, B. H.; Li, Z. J.; Shi, N.; Xu, X. L.; Zhang, K.; Fang, Y.
X. Youji Huaxue 2009, 29, 770; (e) Shi, D. Q.; Ni, S. N.; Yang, F.; Ji, S.
J. J Heterocycl Chem 2008, 45, 1275; (f) Valizadeh, H.; Shockravi, A.;
Gholipur, H. J Heterocycl Chem 2007, 44, 867.
Acknowledgments. The authors are grateful to the National
Natural Science foundation of China (20802061), the Natural
Science foundation (08KJD150019), and Qing Lan Project
(08QLT001) of Jiangsu Education Committee for financial
support.
[7] (a) Wang, X. S.; Zhang, M. M.; Jiang, H.; Shi, D. Q.; Tu,
S. J.; Wei, X. Y.; Zong, Z. M. Synthesis 2006, 4187; (b) Wang, X. S.;
Zhang, M. M.; Jiang, H.; Yao, C. S.; Tu, S. J. Tetrahedron 2007, 63,
4439; (c) Wang, X. S.; Wu, J. R.; Li, Q.; Yao, C. S.; Tu, S. J. Synlett
2008, 1185; (d) Wang, X. S.; Zhang, M. M.; Shi, D. Q.; Tu, S. J.;
Wei, X. Y.; Zong, Z. M. J Heterocycl Chem 2008, 45, 71; (e) Wang,
X. S.; Wu, J. R.; Li, Q.; Zhang, M. M. J Heterocycl Chem 2009, 46,
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet