Triethylamine-catalyzed domino reactions of 1,3-thiazolidinedione: A facile access to functionalized dihydrothiophenes

Article abstract of DOI:10.1002/ejoc.200900845

In the presence of triethylamine as base catalyst, aromatic amines have successfully been used as substrates in the domino reactions of 1,3-thiazolidinedione, malononitrile, and aromatic aldehydes. Through a domino ring-opening/recyclization process of 1,

Full text of DOI:10.1002/ejoc.200900845

FULL PAPER
DOI: 10.1002/ejoc.200900845
Triethylamine-Catalyzed Domino Reactions of 1,3-Thiazolidinedione:
A Facile Access to Functionalized Dihydrothiophenes
Jing Sun,[a] Er-Yan Xia,[a] Li-Li Zhang,[a] and Chao-Guo Yan*[a]
Keywords: Domino reactions / Multicomponent reactions / Cyclization / Heterocycles / Amines
In the presence of triethylamine as base catalyst, aromatic
amines have successfully been used as substrates in the dom-
been synthesized in high yields. Dihydrothiophene deriva-
tives can be converted efficiently into the corresponding thio-
ino reactions of 1,3-thiazolidinedione, malononitrile, and aro- phenes by oxidation with DDQ under mild conditions.
matic aldehydes. Through a domino ring-opening/recycliza-
tion process of 1,3-thiazolidinedione, a series of polysubsti-
tuted dihydrothiophenes in the trans configuration have
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Multicomponent reactions (MCRs) involving domino obtain more information about the mechanism of this
processes, with at least three different substrates reacting in multicomponent reaction and to examine the substrate
a well-dened manner to form a single compound, have scope and its limitations, we have investigated the reactivity
emerged as a powerful tool in organic synthesis.[1,2] In re- of versatile amines in the reaction and found very interest-
cent years MCRs have attracted considerable attention due ing results. Herein we wish to report the reactivity of aro-
to their rapid elaboration of complex structures in a highly matic amines in the above-mentioned multicomponent reac-
efficient and modular manner, and the formation of several tions.
bonds in a single step is highly compatible with the goals
of “green chemistry” and atom economy.[3,4] The applica-
tion of this strategy in the synthesis of heterocycles has re-
cently become an attractive field because of the important
Results and Discussion
role of these targets in natural products, pharmaceuticals,
In the four-component reactions of 1,3-thiazolidine-
and functional materials.[5,6] The synthesis of heterocycles dione, malononitrile, aromatic aldehydes, and amines we
by multicomponent reactions often involves classic car- found that the structure of the amine played an important
bonyl condensation chemistry.[7,8] Among carbonyl com- role. Secondary amines such as pyrrolidine, piperidine,
pounds, 1,3-dicarbonyl derivatives are important synthetic morpholine, and dimethylamine and primary amines such
intermediates, incorporating multiple functionalities that as benzylamine yield dihydrothiophene derivatives by a
can act as either nucleophilic or electrophilic species in a domino ring-opening/recyclization reaction of 1,3-thiazol-
variety of synthetic transformations.[9] The high synthetic idinedione.[11] It was very interesting to investigate the reac-
potential of these easily accessible reagents has found nu- tivity of aromatic amines in this multicomponent reaction.
merous applications, especially in the synthesis of complex At first p-toluidine was chosen as a substrate for the reac-
heterocyclic structures. 1,3-Thiazolidinedione is a heterocy- tion. When equimolar amounts of benzaldehyde, malono-
clic compound with an active methylene group that has nitrile, 1,3-thiazolidinedione, and p-toluidine in acetonitrile
been used in many condensation reactions.[10–13] Recently were stirred at room temperature for 2 days, a complex mix-
we reported a novel domino reaction involving 1,3-thiazol- ture of products was formed from which Knoevenagel con-
idinedione, malononitrile, aromatic aldehydes, and densation products of benzaldehyde with malononitrile and
amines.[14] The reaction is unique because the ring-opening/ benzaldehyde with 1,3-thiazolidinedione among others were
recyclization or spiro-cyclization process unexpectedly oc- detected. This result means that the basicity of the aromatic
curs at the 1,3-thiazolidinedione ring with different kinds amine is probably too weak to promote the ring cleavage of
of amines, and dihydrothiophene or spirocyclohexane[1,3]- 1,3-thiazolidinedione. Other base catalysts, such as sodium
thiazole derivatives, which are normally difficult to pre- and potassium carbonate and pyridine, were added to the
pare,[15–17] are obtained in a very convenient manner. To reaction and some expected products were formed along
with some byproducts. The best result was obtained by add-
[a] College of Chemistry & Chemical Engineering, Yangzhou
ing triethylamine as a base catalyst, which gave the dihy-
drothiophene derivative 1a in about 20% yield after 4 days
at room temperature. At an elevated temperature (40–
University,
Yangzhou 225002, P. R. China
E-mail Address: cgyan@yzu.edu.cn
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J. Sun, E.-Y. Xia, L.-L. Zhang, C.-G. Yan
FULL PAPER
50 °C) the yield of 1a (Table 1, entry 1) was increased to the 2- and 3-positions of the dihydrothiophene ring display
47% and at reflux a complex mixture was formed. Thus, two singlets at 4.60 and 4.20 ppm. The 1H NMR spectra of
with triethylamine as the base catalyst and p-toluidine as a the other dihydrothiophenes also show two singlets or
nucleophile, the domino ring-opening/recyclization reaction slightly broad peaks at around 4.60 and 4.20 ppm for the
of 1,3-thiazolidinedione with benzaldehyde and malono- two protons at the 2- and 3-positions of the thiophene ring,
nitrile took place smoothly at 50 °C. Encouraged by these which strongly suggests that only one stereoisomer of the
results, we investigated the reactions of various aromatic product exists. The molecular structures of the six dihy-
aldehydes with different substituents under these optimal drothiophenes determined by X-ray diffraction also clearly
reaction conditions. The results are collected in Table 1 and show that the two substituents at the 2- and 3-positions are
show that all of the reactions proceeded smoothly to afford in a trans configuration and that the 4-cyano and 5-amino
the corresponding dihydrothiophenes 1b–1i in moderate-to- groups are connected to a C=C double bond. The molecu-
good yields (38–72%). Aromatic aldehydes carrying either lar structure of 2c is shown in Figure 1. Thus, we can con-
electron-donating or -withdrawing substituents showed sim- clude that only trans dihydrothiophenes were produced in
ilar reactivity and reacted efficiently to yield the desired di- the reaction and that this four-component reaction is a dia-
hydrothiophene as the main product. Thus, our present pro- stereoselective reaction. Note that under these new reaction
tocol provides an expedient method for the synthesis of di- conditions aromatic amines usually gave higher yields of
hydrothiophene compounds.[15–17]
dihydrothiophenes than the aliphatic amines studied in our
previous work.[14]
Table 1. Synthesis of dihydrothiophenes by one-pot four-compo-
nent reactions.
Table 2. Synthesis of dihydrothiophenes by one-pot four-compo-
nent reactions.
Entry
ArЈ
Ar
Yield [%]
Entry
ArЈ
Ar
Yield [%]
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
Ph
47
65
47
66
72
51
54
66
38
p-H3CC6H4
p-(CH3)2CHC6H4
p-HOC6H4
p-H3COC6H4
p-FC6H4
p-ClC6H4
p-BrC6H4
m-O2NC6H4
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
Ph
Ph
Ph
Ph
α-Naph
o-ClC6H4
m-ClC6H4
2,4-Cl2C6H4
p-O2NC6H4
Ph
54
62
57
67
44
50
80
75
79
60
78
56
57
28
p-CH3OC6H4
p-FC6H4
p-ClC6H4
m-O2NC6H4
Ph
p-CH3OC6H4
p-ClC6H4
9
p-BrC6H4
10
11
12
13
14
p-CH3OC6H4
p-CH3OC6H4
p-CH3OC6H4
p-CH3OC6H4
p-CH3OC6H4
To further explore the scope of this four-component re-
action, a variety of substituted arylamines were tested un-
der the optimal reaction conditions. The results are summa-
rized in Table 2. In general, aniline and arylamines contain-
ing p-chloro, m-chloro, and 2,4-dichloro groups, as well as
α-naphthylamine, gave dihydrothiophene derivatives 2a–2m
This domino reaction proceeds in a very straightforward
in acceptable yields. But p-nitroaniline gave a very low yield manner. To explain the formation of dihydrothiophenes by
of the product 2n (28%), which might be due to the very this one-pot domino multicomponent reaction, we have
low nucleophilicity of p-nitroaniline caused by the strongly proposed a plausible reaction mechanism, which is illus-
electron-withdrawing nitro group. The structures of the pre- trated in Scheme 1. The first step is the deprotonation of
pared dihydrothiophenes 1a–1i and 2a–2m were determined 1,3-thiazolidinedione by triethylamine to form a carbanion
1
by elemental analysis and H and 13C NMR, MS, and IR intermediate and the formation of arylidenemalononitrile A
spectroscopy, which were further confirmed by single-crys- derived from the Knoevenagel condensation of an aromatic
tal X-ray diffraction studies performed on the representa- aldehyde with malononitrile catalyzed by triethylamine. The
1
tive compounds 1e, 2c, 2f, 2i, 2j, and 2l. In the H NMR second step is the Michael addition of the carbanion of 1,3-
spectrum of dihydrothiophene 1a the 5-amino group shows thiazolidinedione to arylidenemalononitrile A to yield the
a singlet at 7.19 ppm and the two NH units display two adduct B. The arylamine then attacks the carbonyl group
broad peaks at 10.66 and 10.15 ppm. The two protons at of thiazolidinedione in a ring-opening reaction to give a
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Facile Access to Functionalized Dihydrothiophenes
Figure 1. The molecular structure of 2c.
Scheme 1. Proposed mechanism for the formation of polyfunctional dihydrothiophenes.
sulfide anion C, which intramolecularly nucleophilically at- of the two protons at the 2- and 3-positions of the corre-
tacks one of the cyano groups to form sulfur-containing sponding dihydrothiophene. Note that the amino group in
five-membered ring intermediate D. Finally, the 2,3-dihy- 3c shows a singlet at δ = 8.13 ppm, which is greatly shifted
drothiophene is produced through an imine–enamine tauto- to a lower magnetic field relative to the signal of the amino
merization process. In the cyclization step the sterically group in the corresponding dihydrothiophene 1h (δ =
large 4-aryl and 5-ureidoformamide groups would prefer 7.25 ppm). The single-crystal structures of 3a (Figure 2)
stereochemically opposite positions to reduce the steric hin- and 3e also reveal the formation of the thiophene ring. In
drance in the sulfide anion C and in the transition state the molecular structure of 3e the two C=C double bond
of the cyclization step. Thus, only the trans isomeric 2,3- lengths of C12–C13 and C11–C15 are 1.393(2) and
dihydrothiophene was produced after cyclization. In this 1.375(2) Å, and the two C–S bond lengths are 1.7510(19)
proposed reaction mechanism triethylamine acts as a base and 1.7265(19) Å.
to catalyze the Knoevenagel condensation and Michael ad-
dition reaction, whereas the arylamine behaves as a nucleo-
philic reagent to complete the intermolecular substitution
reaction.
Table 3. Synthesis of thiophenes by dehydrogenation.
We were interested in exploring the aromatization of the
above prepared dihydrothiophenes to thiophenes. By using
DDQ as the oxidant, the suspensions of some representa-
tive dihydrothiophenes were stirred in acetonitrile at 35–
40 °C for several hours, which gave the corresponding thio-
phenes 3a–3e efficiently in very high yields (Table 3). Thus,
this protocol provides an expedient method for the synthe-
sis of polysubstituted thiophene derivatives. The H NMR
spectra of thiophenes 3a–3e clearly show the disappearance
Entry
ArЈ
Ar
Yield [%]
1
2
3
4
5
3a
3b
3c
3d
3e
Ph
p-ClC6H4
p-ClC6H4
p-BrC6H4
p-BrC6H4
m-O2NC6H4
93
95
94
95
90
p-ClC6H4
p-CH3C6H4
Ph
1
p-ClC6H4
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J. Sun, E.-Y. Xia, L.-L. Zhang, C.-G. Yan
FULL PAPER
Figure 2. The molecular structure of 3a.
δ = 172.3, 161.7, 150.5, 141.5, 134.9, 132.8, 129.3, 128.7, 127.5,
Conclusions
127.1, 119.8, 118.1, 70.4, 55.3, 51.6, 20.3, 18.6 ppm. IR (KBr): ν =
˜
We have extended the scope of the previously discovered
tandem reactions of 1,3-thiazolidinedione, malononitrile,
aromatic aldehydes, and amines. Polysubstituted dihydroth-
iophenes with a trans configuration and the corresponding
thiophene derivatives have been efficiently prepared in mod-
erate yields by a domino ring-opening/recyclization reaction
of 1,3-thiazolidinedione. The advantages of this approach
are as follows: The reaction procedure is convenient, involv-
ing a simple experimental procedure and product isolation,
thus dispensing with extensive recrystallization or chroma-
tographic purification steps. It is a four-component reaction
that allows the construction of relatively complex sulfur-
containing heterocyclic systems by using simple starting
materials. Thus, our present protocol provides an expedient
method for the diastereomeric synthesis of dihydrothio-
phene compounds.
3439, 3304, 3200, 2983, 2199, 1712, 1689, 1638, 1595, 1548, 1514,
1453, 1408, 1384, 1353, 1317, 1295, 1255, 1240, 1198, 974, 836,
813, 796 cm–1. MS: m/z (%) = 378.00 (100) [M – 1]+. C20H18N4O2S
(378.45): calcd. C 63.47, H 4.79, N 14.80; found C 63.45, H 5.08,
N 14.51.
1b: White solid, 65%, m.p. 246–248 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.68 (br. s, 1 H, NH), 10.16 (br. s, 1 H, NH), 7.42
(d, J = 8.4 Hz, 2 H, ArH), 7.22–7.16 (m, 6 H, ArH, NH2), 7.13 (d,
J = 8.4 Hz, 2 H, ArH), 4.57 (d, J = 2.4 Hz, 1 H, CH), 4.17 (s, 1
H, CH), 2.30 (s, 3 H, CH3), 2.26 (s, 3 H, CH3) ppm. 13C NMR
(150 MHz, [D6]DMSO): δ = 172.3, 161.5, 150.5, 138.4, 136.7,
134.8, 132.9, 129.3, 129.2, 127.0, 119.8, 118.1, 70.6, 55.4, 51.3, 20.6,
20.3 ppm. IR (KBr): ν = 3431, 3304, 3192, 2987, 2202, 1714, 1691,
˜
1639, 1591, 1551, 1513, 1409, 1383, 1350, 1318, 1294, 1241, 1197,
1109, 1023, 975, 887, 813, 798, 756 cm–1. MS: m/z (%) = 391.58
(100) [M – 1]+. C21H20N4O2S (392.47): calcd. C 64.27, H 5.14, N
14.28; found C 64.12, H 5.43, N 14.45.
1c: White solid, 47%, m.p. Ͼ250 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.68 (br. s, 1 H, NH), 10.19 (br. s, 1 H, NH), 7.43
(d, J = 7.8 Hz, 2 H, ArH), 7.25 (s, 4 H, ArH), 7.18 (s, 2 H, NH2),
7.14 (d, J = 7.8 Hz, 2 H, ArH), 4.59 (d, J = 3.0 Hz, 1 H, CH), 4.20
(s, 1 H, CH), 2.92–2.85 (m, 1 H, CH), 2.26 (s, 3 H, CH3), 1.20 (d,
J = 6.6 Hz, 6 H, CH3) ppm. 13C NMR (150 MHz, [D6]DMSO): δ
= 172.3, 161.5, 150.5, 147.4, 138.9, 134.9, 132.9, 129.3, 127.0, 126.6,
Experimental Section
General Procedure for the Preparation of Dihydrothiophenes by a
One-Pot Four-Component Reaction of 1,3-Thiazolidinedione, Aro-
matic Aldehydes, Malononitrile, and p-Toluidine: A mixture of aro-
matic aldehyde (4.0 mmol), malononitrile (4.0 mmol, 0.264 g), and
triethylamine (1.0 mmol, 0.101 g) in acetonitrile (5.0 mL) was
stirred at room temperature for 2 min. Then p-toluidine (4.0 mmol,
0.428 g) and 1,3-thiazolidinedione (4.0 mmol) were added and the
reaction was stirred at 40 °C for an additional 48 h. The resulting
precipitate was collected by filtration and washed with acetonitrile.
The crude product was recrystallized with a mixture of acetonitrile
and N,N-dimethylformamide to give the pure products 1a–1i.
119.8, 118.2, 70.5, 55.3, 51.3, 33.1, 23.8, 20.4 ppm. IR (KBr): ν =
˜
3436, 3363, 3296, 3231, 3187, 2959, 2203, 1711, 1686, 1638, 1594,
1550, 1510, 1410, 1315, 1237, 1194, 1053, 974, 815, 795 cm–1. MS:
m/z (%) = 419.71 (100) [M – 1]+. C23H24N4O2S (420.53): calcd. C
65.69, H 5.75, N 13.32; found C 65.84, H 5.90, N 13.11.
1d: White solid, 66%, m.p. 245–246 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.68 (br. s, 1 H, NH), 10.18 (br. s, 1 H, NH), 9.38
(s, 1 H, OH), 7.42 (d, J = 8.4 Hz, 2 H, ArH), 7.14–7.12 (m, 6 H,
1a: White solid, 47%, m.p. Ͼ250 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.66 (br. s, 1 H, NH), 10.15 (br. s, 1 H, NH), 7.42– ArH, NH2), 6.77 (d, J = 8.4 Hz, 2 H, ArH), 4.53 (d, J = 2.4 Hz, 1
7.37 (m, 4 H, ArH), 7.34–7.29 (m, 3 H, ArH), 7.19 (s, 2 H, NH2), H, CH), 4.15 (s, 1 H, CH), 2.26 (s, 3 H, CH3) ppm. 13C NMR
7.13 (d, J = 7.8 Hz, 2 H, ArH), 4.60 (s, 1 H, CH), 4.20 (s, 1 H, (150 MHz, [D6]DMSO): δ = 172.4, 161.2, 156.8, 150.5, 134.8,
CH), 2.26 (s, 3 H, CH3) ppm. 13C NMR (150 MHz, [D6]DMSO):
132.9, 131.6, 129.3, 128.1, 119.8, 118.2, 115.4, 71.0, 55.6, 51.2,
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Facile Access to Functionalized Dihydrothiophenes
20.4 ppm. IR (KBr): ν = 3454, 3420, 3330, 3233, 3119, 2978, 2182,
69.5, 55.1, 50.8, 20.3 ppm. IR (KBr): ν = 3435, 3311, 3234, 3205,
˜
˜
1705, 1676, 1596, 1547, 1512, 1444, 1407, 1358, 1315, 1251, 1234,
1202, 1175, 1124, 1102, 970, 902, 821, 806, 791, 764 cm–1. MS: m/z
(%) = 393.56 (100) [M – 1]+. C20H18N4O3S (394.45): calcd. C 60.90,
H 4.60, N 14.20; found C 60.85, H 4.77, N 14.05.
3129, 2980, 2200, 1712, 1691, 1650, 1598, 1555, 1525, 1408, 1351,
1241, 1188, 1121, 1099, 1081, 983, 932, 868, 814 cm–1. MS: m/z (%)
= 422.48 (100) [M – 1]+. C20H17N5O4S (423.45): calcd. C 56.73, H
4.05, N 16.54; found C 56.51, H 3.84, N 16.27.
1
1e: White solid, 72%, m.p. 222–224 °C. H NMR (600 MHz, [D6]-
General Procedure for the Preparation of Dihydrothiophenes by a
One-Pot Four-Component Reaction of 1,3-Thiazolidinedione, Aro-
matic Aldehyde, Malononitrile, and Arylamine: A mixture of aro-
DMSO): δ = 10.67 (br. s, 1 H, NH), 10.17 (br. s, 1 H, NH), 7.42
(d, J = 7.8 Hz, 2 H, ArH), 7.24 (d, J = 8.4 Hz, 2 H, ArH), 7.16–
7.13 (m, 4 H, ArH, NH2), 6.94 (d, J = 8.4 Hz, 2 H, ArH), 4.56 (s, matic aldehyde (4.0 mmol), malononitrile (4.0 mmol, 0.264 g), and
1 H, CH), 4.15 (s, 1 H, CH), 3.75 (s, 3 H, OCH3), 2.26 (s, 3 H, triethylamine (1.0 mmol, 0.101 g) in acetonitrile (5.0 mL) was
CH3) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 172.3, 161.3,
158.7, 150.5, 134.8, 133.3, 132.8, 129.3, 128.2, 119.8, 118.2, 114.1,
stirred at room temperature for 2 min. Then arylamine (4.0 mmol)
and 1,3-thiazolidinedione (4.0 mmol) were added and the reaction
was stirred at 40 °C for an additional 48 h. The resulting precipitate
was collected by filtration and washed with acetonitrile. The crude
product was recrystallized with a mixture of acetonitrile and N,N-
dimethylformamide to give the pure products 2a–2n.
2a: White solid, 54%, m.p. 246–247 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.85 (br. s, 1 H, NH), 10.35 (br. s, 1 H, NH), 7.61
(d, J = 7.8 Hz, 2 H, ArH), 7.41–7.39 (m, 4 H, ArH), 7.35–7.30 (m,
3 H, ArH), 7.27 (s, 2 H, NH2), 4.61 (d, J = 1.8 Hz, 1 H, CH), 4.17
70.8, 55.5, 55.1, 51.0, 20.3 ppm. IR (KBr): ν = 3343, 3303, 3135,
˜
2977, 2195, 1705, 1671, 1600, 1547, 1509, 1409, 1349, 1301, 1232,
1194, 1175, 1031, 968, 820 cm–1. MS: m/z (%) = 407.58 (100) [M –
1]+. C21H20N4O3S (408.47): calcd. C 61.75, H 4.94, N 13.72; found
C 61.63, H 5.36, N 13.39.
1
1f: White solid, 51%, m.p. 244–246 °C. H NMR (600 MHz, [D6]-
DMSO): δ = 10.78 (br. s, 1 H, NH), 10.26 (br. s, 1 H, NH), 7.43
(d, J = 7.2 Hz, 2 H, ArH), 7.39–7.37 (m, 2 H, ArH), 7.30 (s, 2 H,
NH2), 7.23 (t, J = 8.4 Hz, 2 H, ArH), 7.14 (d, J = 8.4 Hz, 2 H, (s, 1 H, CH) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 172.3,
ArH), 4.62 (d, J = 2.4 Hz, 1 H, CH), 4.12 (s, 1 H, CH), 2.27 (s, 3
161.7, 150.6, 141.5, 136.4, 128.7, 127.5, 127.1, 121.5, 118.1, 70.5,
H, CH3) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 172.2, 162.4, 55.3, 51.5 ppm. IR (KBr): ν = 3438, 3302, 3197, 3127, 2978, 2201,
˜
161.8, 160.7, 150.5, 137.6, 134.9, 132.9, 129.3, 129.1, 129.0, 119.8,
1709, 1693, 1638, 1594, 1546, 1513, 1493, 1454, 1402, 1351, 1310,
1254, 1235, 1192, 1094, 1011, 973, 828, 767 cm–1. MS: m/z (%) =
397.76 (100) [M – 1]+, 399.49 (18) [M + 1]+. C19H15ClN4O2S
(398.87): calcd. C 57.21, H 3.79, N 14.05; found C 57.53, H 4.27,
N 13.70.
2b: White solid, 62%, m.p. 220–222 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.75 (br. s, 1 H, NH), 10.28 (br. s, 1 H, NH), 7.59
118.1, 115.5, 115.4, 70.4, 55.4, 50.8, 20.3 ppm. IR (KBr): ν = 3424,
˜
3326, 3228, 3159, 2971, 2188, 1719, 1681, 1623, 1597, 1575, 1544,
1503, 1408, 1384, 1349, 1314, 1256, 984, 885, 817, 789 cm–1. MS:
m/z (%) = 395.67 (100) [M – 1]+. C20H17FN4O2S (396.44): calcd.
C 60.59, H 4.32, N 14.13; found C 60.44, H 4.69, N 13.86.
1g: White solid, 54%, m.p. 246–248 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.68 (br. s, 1 H, NH), 10.17 (br. s, 1 H, NH), 7.46– (d, J = 9.0 Hz, 2 H, ArH), 7.38 (d, J = 9.0 Hz, 2 H, ArH), 7.25 (d,
7.42 (m, 4 H, ArH), 7.37 (d, J = 8.4 Hz, 2 H, ArH), 7.26 (s, 2 H, J = 8.4 Hz, 2 H, ArH), 7.16 (s, 2 H, NH2), 6.94 (d, J = 8.4 Hz, 2
NH2), 7.14 (d, J = 8.4 Hz, 2 H, ArH), 4.63 (br. s, 1 H, CH), 4.19
(s, 1 H, CH), 2.27 (s, 3 H, CH3) ppm. 13C NMR (150 MHz, [D6]-
DMSO): δ = 172.1, 162.0, 150.5, 140.4, 134.8, 132.9, 132.2, 129.3,
H, ArH), 4.56 (d, J = 2.4 Hz, 1 H, CH), 4.15 (s, 1 H, CH), 3.75 (s,
3 H, OCH3) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 172.3,
161.3, 158.7, 150.6, 136.4, 133.3, 128.7, 128.2, 127.5, 121.5, 118.2,
129.0, 128.7, 119.8, 118.0, 70.2, 55.2, 50.9, 20.4 ppm. IR (KBr): ν
114.1, 70.8, 55.5, 55.1, 51.0 ppm. IR (KBr): ν = 3424, 3336, 3302,
˜
˜
= 3408, 3314, 3192, 3136, 2983, 2889, 2208, 1893, 1713, 1687, 1660,
1599, 1555, 1514, 1489, 1409, 1359, 1316, 1297, 1241, 1191, 1122,
1088, 1014, 981, 937, 877, 816, 790, 761 cm–1. MS: m/z (%) = 411.43
(100) [M – 1]+, 413.38 (28) [M + 1]+. C20H17ClN4O2S (412.89):
calcd. C 58.18, H 4.15, N 13.57; found C 57.70, H 4.36, N 13.29.
3228, 3143, 2964, 2837, 2179, 1716, 1678, 1633, 1594, 1570, 1539,
1494, 1402, 1357, 1334, 1307, 1252, 1217, 1180, 1116, 1093, 1027,
978, 884, 823, 791, 752 cm–1. MS: m/z (%) = 427.67 (100) [M –
1]+, 429.62 (37) [M + 1]+. C20H17ClN4O3S (428.89): calcd. C 56.01,
H 4.00, N 13.06; found C 55.74, H 4.28, N 12.75.
1h: White solid, 66%, m.p. 249–250 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.68 (br. s, 1 H, NH), 10.15 (br. s, 1 H, NH), 7.59
2c: Yellow solid, 57%, m.p. 232–234 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.74 (br. s, 1 H, NH), 10.27 (br. s, 1 H, NH), 7.60
(d, J = 8.4 Hz, 2 H, ArH), 7.42 (d, J = 7.8 Hz, 2 H, ArH), 7.31 (d, (d, J = 8.4 Hz, 2 H, ArH), 7.39–7.37 (m, 4 H, ArH), 7.23–7.20 (m,
J = 8.4 Hz, 2 H, ArH), 7.25 (s, 2 H, NH2), 7.14 (d, J = 8.4 Hz, 2 4 H, ArH, NH2), 4.62 (br. s, 1 H, CH), 4.18 (s, 1 H, CH) ppm. 13
H, ArH), 4.60 (d, J = 2.4 Hz, 1 H, CH), 4.18 (s, 1 H, CH), 2.26 (s, 3 NMR (150 MHz, [D6]DMSO): δ = 172.2, 162.4, 161.8, 160.7,
H, CH3) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 172.1, 162.0, 150.6, 137.5, 136.4, 129.1, 129.0, 128.7, 127.5, 121.4, 118.1, 115.5,
C
150.5, 140.9, 134.8, 132.9, 131.6, 129.4, 129.3, 120.6, 119.8, 118.0,
115.4, 70.4, 55.4, 50.8 ppm. IR (KBr): ν = 3455, 3346, 3303, 3233,
˜
70.0, 55.1, 51.0, 20.4 ppm. IR (KBr): ν = 3726, 3667, 3643, 3406,
3119, 2982, 2191, 1705, 1672, 1594, 1548, 1513, 1401, 1354, 1306,
1250, 1230, 1210, 1117, 1092, 1011, 971, 938, 905, 830, 804,
766 cm–1. MS: m/z (%) = 415.34 (100) [M – 1]+. C19H14ClFN4O2S
(416.86): calcd. C 54.74, H 3.39, N 13.44; found C 54.90, H 3.56,
N 13.07.
2d: White solid, 67%, m.p. 233–234 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.75 (br. s, 1 H, NH), 10.27 (br. s, 1 H, NH), 7.60
(d, J = 8.4 Hz, 2 H, ArH), 7.46 (d, J = 8.4 Hz, 2 H, ArH), 7.38 (d,
˜
3345, 3312, 3191, 3133, 2979, 2351, 2317, 2194, 1893, 1713, 1688,
1660, 1599, 1554, 1515, 1486, 1406, 1355, 1316, 1240, 1189, 1119,
1070, 1010, 979, 937, 879, 816, 790, 759 cm–1. MS: m/z (%) = 455.39
(100) [M – 1]+, 457.39 (97) [M + 1]+. C20H17BrN4O2S (457.34):
calcd. C 52.52, H 3.75, N 12.25; found C 52.30, H 3.94, N 11.87.
1i: Yellow solid, 38%, m.p. Ͼ250 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.67 (br. s, 1 H, NH), 10.17 (br. s, 1 H, NH), 8.24
(br. s, 1 H, ArH), 8.20–8.18 (m, 1 H, ArH), 7.83 (d, J = 7.8 Hz, 1 J = 7.8 Hz, 4 H, ArH), 7.25 (s, 2 H, NH2), 4.62 (br. s, 1 H, CH),
H, ArH), 7.22 (t, J = 7.8 Hz, 1 H, ArH), 7.43 (d, J = 7.8 Hz, 2 H,
4.18 (s, 1 H, CH) ppm. 13C NMR (150 MHz, [D6]DMSO): δ =
ArH), 7.37 (s, 2 H, NH2), 7.14 (d, J = 8.4 Hz, 2 H, ArH), 4.78 (br. 172.1, 162.0, 150.6, 140.4, 136.4, 132.2, 129.0, 128.7, 128.6, 127.6,
s, 1 H, CH), 4.23 (br. s, 1 H, CH), 2.27 (s, 3 H, CH3) ppm. 13C 121.4, 118.0, 70.1, 55.2, 50.9 ppm. IR (KBr): ν = 3390, 3305, 3222,
˜
NMR (150 MHz, [D6]DMSO): δ = 172.0, 162.7, 150.6, 148.1,
143.7, 134.9, 134.0, 132.9, 130.3, 129.3, 122.6, 121.9, 119.8, 117.9,
3156, 2964, 2179, 1709, 1692, 1633, 1595, 1552, 1490, 1403, 1359,
1302, 1280, 1217, 1180, 1088, 1011, 975, 886, 822, 766 cm–1. MS:
Eur. J. Org. Chem. 2009, 5247–5254
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5251

J. Sun, E.-Y. Xia, L.-L. Zhang, C.-G. Yan
m/z (%) = 431.38 (100) [M – 1]+, 433.36 (81) [M + 1]+. 50.9 ppm. IR (KBr): ν = 3458, 3297, 3186, 2991, 2199, 1692, 1640,
FULL PAPER
˜
C19H14Cl2N4O2S (433.31): calcd. C 52.67, H 4.26, N 12.93; found
C 52.49, H 3.52, N 12.66.
2e: Yellow solid, 44%, m.p. 247–250 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.75 (br. s, 1 H, NH), 10.28 (br. s, 1 H, NH), 8.25
(s, 1 H, ArH), 8.20–8.19 (m, 1 H, ArH), 7.83 (d, J = 7.8 Hz, 1 H,
1586, 1560, 1497, 1446, 1407, 1384, 1346, 1326, 1313, 1243, 1202,
1178, 1073, 1010, 977, 900, 883, 824, 765, 753 cm–1. MS: m/z (%)
= 441.53 (100) [M – 1]+, 443.61 (98) [M + 1]+. C19H15BrN4O2S
(443.32): calcd. C 51.48, H 3.41, N 12.64; found C 51.33, H 3.79,
N 12.42.
1
ArH), 7.72 (t, J = 7.8 Hz, 1 H, ArH), 7.61 (d, J = 9.0 Hz, 2 H, 2j: White solid, 60%, m.p. 210–212 °C. H NMR (600 MHz, [D6]-
ArH), 7.40–7.38 (m, 4 H, ArH, NH2), 4.79 (s, 1 H, CH), 4.24 (s, 1
H, CH) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 172.0, 162.7,
150.6, 148.1, 143.7, 136.4, 134.0, 130.3, 128.7, 127.5, 122.6, 121.9,
DMSO): δ = 11.04 (s, 2 H, NH), 8.09 (d, J = 6.6 Hz, 1 H, ArH),
8.00–7.99 (m, 2 H, ArH), 7.76 (d, J = 7.8 Hz, 1 H, ArH), 7.71 (t,
J = 7.8 Hz, 1 H, ArH), 7.61 (t, J = 7.2 Hz, 1 H, ArH), 7.53 (t, J
= 7.8 Hz, 1 H, ArH), 7.30–7.27 (m, 4 H, ArH, NH2), 6.97–6.96
(m, 2 H, ArH), 4.65 (d, J = 2.4 Hz, 1 H, CH), 4.19 (s, 1 H, CH),
3.76 (s, 3 H, OCH3) ppm. 13C NMR (150 MHz, [D6]DMSO): δ =
173.1, 161.4, 158.7, 151.0, 133.6, 133.4, 132.4, 128.6, 128.2, 126.7,
126.2, 125.8, 125.6, 124.5, 120.4, 118.3, 118.2, 114.1, 70.9, 55.6,
121.4, 117.9, 69.5, 55.1, 50.7 ppm. IR (KBr): ν = 3437, 3310, 3233,
˜
3129, 2980, 2200, 1715, 1692, 1649, 1596, 1552, 1525, 1492, 1403,
1350, 1307, 1255, 1235, 1187, 1095, 1010, 981, 931, 828, 807, 773,
751 cm–1. MS: m/z (%) = 442.66 (100) [M – 1]+. C19H14ClN5O4S
(443.86): calcd. C 51.41, H 3.18, N 15.78; found C 51.28, H 3.65,
N 15.49.
55.1, 51.1 ppm. IR (KBr): ν = 3431, 3302, 3198, 2972, 2191, 1710,
˜
1632, 1566, 1510, 1405, 1349, 1304, 1250, 1177, 1031, 987, 794,
770 cm–1. MS: m/z (%) = 443.64 (100) [M – 1]+. C24H20N4O3S
(444.51): calcd. C 64.85, H 4.54, N 12.60; found C 64.57, H 4.80,
N 12.35.
1
2f: White solid, 50%, m.p. 244–246 °C. H NMR (600 MHz, [D6]-
DMSO): δ = 10.81 (br. s, 1 H, NH), 10.33 (br. s, 1 H, NH), 7.55
(d, J = 7.8 Hz, 2 H, ArH), 7.40 (t, J = 7.2 Hz, 2 H, ArH), 7.35–
7.30 (m, 5 H, ArH), 7.27 (s, 2 H, NH2), 7.10 (t, J = 7.2 Hz, 1 H,
ArH), 4.61 (d, J = 2.4 Hz, 1 H, CH), 4.17 (s, 1 H, CH) ppm. 13C 2k: White solid, 78%, m.p. 206–208 °C. 1H NMR (600 MHz,
NMR (150 MHz, [D6]DMSO): δ = 172.3, 161.7, 150.5, 141.5,
137.4, 128.9, 128.7, 127.5, 127.1, 123.8, 119.8, 118.2, 70.5, 55.3,
[D6]DMSO): δ = 10.98 (s, 1 H, NH), 10.83 (s, 1 H, NH), 8.24 (d,
J = 8.4 Hz, 1 H, ArH), 7.54 (d, J = 7.2 Hz, 1 H, ArH), 7.35 (t, J
= 7.8 Hz, 1 H, ArH), 7.26 (d, J = 8.4 Hz, 2 H, ArH), 7.17–7.13
(m, 3 H, ArH, NH2), 6.95 (d, J = 8.4 Hz, 2 H, ArH), 4.57 (d, J =
51.6 ppm. IR (KBr): ν = 3432, 3300, 3188, 2989, 2200, 1716, 1699,
˜
1638, 1592, 1551, 1524, 1448, 1384, 1350, 1329, 1256, 1201, 1079,
993, 973, 889, 837, 775, 756 cm–1. MS: m/z (%) = 363.40 (100) [M –
1]+. C19H16N4O2S (364.42): calcd. C 62.62, H 4.43, N 15.37; found
C 62.48, H 4.72, N 15.04.
2.4 Hz, 1 H, CH), 4.15 (s, 1 H, CH), 3.76 (s, 3 H, OCH3) ppm. 13
C
NMR (150 MHz, [D6]DMSO): δ = 172.8, 161.3, 158.7, 150.5,
134.5, 133.3, 129.3, 128.2, 127.8, 124.8, 122.4, 121.3, 118.2, 114.1,
70.8, 55.5, 55.1, 51.0 ppm. IR (KBr): ν = 3442, 3310, 3202, 2195,
˜
2g: Light-yellow solid, 80%, m.p. 217–219 °C. 1H NMR (600 MHz,
[D6]DMSO): δ = 10.71 (br. s, 1 H, NH), 10.24 (br. s, 1 H, NH),
7.54 (d, J = 7.8 Hz, 2 H, ArH), 7.33 (t, J = 7.8 Hz, 2 H, ArH),
7.25 (d, J = 8.4 Hz, 2 H, ArH), 7.16 (s, 2 H, NH2), 7.10 (t, J =
7.2 Hz, 1 H, ArH), 6.95 (d, J = 8.4 Hz, 2 H, ArH), 4.57 (d, J =
1710, 1676, 1643, 1583, 1537, 1511, 1462, 1361, 1289, 1247, 1215,
1177, 1062, 1033, 973, 887, 828 cm–1. MS: m/z (%) = 427.59 (100)
[M – 1]+, 429.42 (39) [M + 1]+. C20H17ClN4O3S (428.89): calcd. C
56.01, H 4.00, N 13.06; found C 56.37, H 4.29, N 12.77.
1
2.4 Hz, 1 H, CH), 4.16 (s, 1 H, CH), 3.75 (s, 3 H, OCH3) ppm. 13
C
2l: White solid, 56%, m.p. 225–228 °C. H NMR (600 MHz, [D6]-
NMR (150 MHz, [D6]DMSO): δ = 171.3, 160.3, 157.6, 149.4,
136.3, 132.2, 127.8, 127.1, 122.7, 118.7, 117.1, 116.8, 113.0, 69.7,
DMSO): δ = 10.79 (s, 1 H, NH), 10.33 (s, 1 H, NH), 7.79 (s, 1 H,
ArH), 7.44 (d, J = 8.4 Hz, 1 H, ArH), 7.35 (t, J = 8.4 Hz, 1 H,
ArH), 7.25 (d, J = 8.4 Hz, 2 H, ArH), 7.17–7.15 (m, 3 H, ArH,
NH2), 6.95 (d, J = 9.0 Hz, 2 H, ArH), 4.57 (d, J = 2.4 Hz, 1 H,
CH), 4.17 (s, 1 H, CH), 3.76 (s, 3 H, OCH3) ppm. 13C NMR
(150 MHz, [D6]DMSO): δ = 172.3, 161.3, 158.7, 150.6, 138.9,
133.2, 130.4, 128.2, 123.5, 119.4, 118.3, 118.2, 114.1, 70.8, 55.6,
54.5, 54.0, 50.0 ppm. IR (KBr): ν = 3403, 3342, 3303, 3200, 2996,
˜
2836, 2245, 2190, 1713, 1636, 1591, 1562, 1509, 1476, 1448, 1356,
1309, 1259, 1224, 1160, 1111, 1084, 1031, 979, 887, 828, 790,
761 cm–1. MS: m/z (%) = 393.75 (100) [M – 1]+. C20H18N4O3S
(394.45): calcd. C 60.90, H 4.60, N 14.20; found C 60.66, H 4.83,
N 13.87.
55.1, 51.0 ppm. IR (KBr): ν = 3453, 3306, 3195, 3139, 2986, 2194,
˜
1693, 1640, 1590, 1554, 1508, 1477, 1424, 1348, 1321, 1301, 1278,
1249, 1174, 1105, 1077, 1036, 983, 883, 826, 777 cm–1. MS: m/z (%)
= 427.32 (100) [M – 1]+, 429.31 (29) [M + 1]+. C20H17ClN4O3S
(428.89): calcd. C 56.01, H 4.00, N 13.06; found C 55.82, H 4.43,
N 12.69.
2h: White solid, 75%, m.p. 248–250 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.81 (br. s, 1 H, NH), 10.34 (br. s, 1 H, NH), 7.56
(d, J = 7.2 Hz, 2 H, ArH), 7.47 (d, J = 8.4 Hz, 2 H, ArH), 7.38 (d,
J = 8.4 Hz, 2 H, ArH), 7.36–7.33 (m, 4 H, ArH, NH2), 7.10 (t, J
= 7.2 Hz, 1 H, ArH), 4.62 (br. s, 1 H, CH), 4.15 (s, 1 H, CH) ppm.
1
13C NMR (150 MHz, [D6]DMSO): δ = 172.2, 162.0, 150.5, 140.4, 2m: White solid, 57%, m.p. 222–224 °C. H NMR (600 MHz, [D6]
137.4, 132.1, 129.0, 128.9, 128.7, 123.8, 119.8, 118.0, 70.1, 55.2,
DMSO): δ = 11.05 (s, 1 H, NH), 10.87 (s, 1 H, NH), 8.26 (d, J =
9.0 Hz, 1 H, ArH), 7.71 (d, J = 2.4 Hz, 1 H, ArH), 7.45–7.43 (m,
1 H, ArH), 7.26 (d, J = 9.0 Hz, 2 H, ArH), 7.18 (s, 2 H, NH2),
6.94 (d, J = 8.4 Hz, 2 H, ArH), 4.56 (d, J = 3.0 Hz, 1 H, CH), 4.15
(s, 1 H, CH), 3.76 (s, 3 H, OCH3) ppm. 13C NMR (150 MHz, [D6]-
50.9 ppm. IR (KBr): ν = 3457, 3298, 3226, 3186, 2990, 2200, 1690,
˜
1641, 1587, 1560, 1495, 1446, 1410, 1384, 1344, 1326, 1313, 1242,
1203, 1178, 1089, 1030, 1014, 990, 977, 900, 884, 827, 799, 768,
753 cm–1. MS: m/z (%) = 397.57 [M – 1]+, 419.46 (100) [M – 1 +
Na]+, 421.50 (30) [M + 1 + Na]+. C19H15ClN4O2S (398.87): calcd. DMSO): δ = 172.9, 161.3, 158.7, 150.5, 133.7, 133.3, 128.7, 128.2,
C 57.21, H 3.79, N 14.05; found C 57.16, H 4.05, N 13.72.
127.9, 127.8, 123.3, 122.2, 118.2, 114.1, 70.8, 55.4, 55.1, 51.0 ppm.
IR (KBr): ν = 3434, 3329, 3228, 3160, 2970, 2838, 2180, 1712, 1682,
˜
2i: White solid, 79%, m.p. Ͼ250 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.71 (br. s, 1 H, NH), 10.22 (br. s, 1 H, NH), 7.59
(d, J = 8.4 Hz, 2 H, ArH), 7.54 (d, J = 7.8 Hz, 2 H, ArH), 7.35–
7.31 (m, 4 H, ArH), 7.26 (s, 2 H, NH2), 7.10 (t, J = 7.8 Hz, 1 H,
ArH), 4.61 (d, J = 1.8 Hz, 1 H, CH), 4.19 (s, 1 H, CH) ppm. 13C
NMR (150 MHz, [D6]DMSO): δ = 172.1, 162.0, 150.5, 140.9,
137.4, 131.6, 129.4, 128.9, 123.8, 120.6, 119.8, 118.0, 70.0, 55.1,
1631, 1583, 1536, 1500, 1388, 1346, 1300, 1250, 1219, 1178, 1100,
1061, 1031, 982, 885, 860, 814, 758 cm–1. MS: m/z (%) = 461.48
(100) [M – 1]+, 463.51 (34) [M + 1]+. C20H16Cl2N4O3S (463.34):
calcd. C 51.84, H 3.48, N 12.09; found C 51.79, H 3.50, N 11.69.
2n: Yellow solid, 28%, m.p. 218–220 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.90 (s, 1 H, NH), 10.64 (s, 1 H, NH), 8.22 (d, J =
5252
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5247–5254

Facile Access to Functionalized Dihydrothiophenes
8.4 Hz, 2 H, ArH), 7.84 (d, J = 8.4 Hz, 2 H, ArH), 7.25 (d, J =
1 H, ArH), 8.26 (t, J = 1.8 Hz, 1 H, ArH), 8.24 (s, 2 H, NH2), 7.91
8.4 Hz, 2 H, ArH), 7.17 (s, 2 H, NH2), 6.95 (d, J = 8.4 Hz, 2 H, (d, J = 7.8 Hz, 1 H, ArH), 7.78 (t, J = 7.8 Hz, 1 H, ArH), 7.49 (d,
ArH), 4.57 (s, 1 H, CH), 4.17 (s, 1 H, CH), 3.76 (s, 3 H,
OCH3) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 172.4, 161.3,
158.7, 150.6, 143.8, 142.7, 133.2, 128.2, 124.9, 119.6, 118.2, 114.1,
J = 9.0 Hz, 2 H, ArH), 7.34 (d, J = 9.0 Hz, 2 H, ArH) ppm. 13C
NMR (150 MHz, [D6]DMSO): δ = 167.5, 162.4, 150.8, 147.9,
144.2, 137.0, 136.5, 134.9, 130.5, 129.1, 128.9, 127.8, 124.5, 124.2,
70.8, 55.6, 55.1, 50.9 ppm. IR (KBr): ν = 3449, 3326, 3124, 2972,
121.8, 115.7, 115.2, 112.5, 88.7 ppm. IR (KBr): ν = 3440, 3329,
˜
˜
2195, 1705, 1630, 1557, 1416, 1338, 1310, 1267, 1236, 1169, 1112,
1028, 884, 850, 815, 744 cm–1. MS: m/z (%) = 438.51 (100) [M –
1]+. C20H17N5O5S (439.44): calcd. C 54.66, H 3.90, N 15.94; found
C 54.50, H 4.13, N 15.78.
3247, 2216, 1724, 1633, 1596, 1481, 1405, 1350, 1318, 1265, 1218,
1181, 1097, 828, 735 cm–1. MS: m/z (%) = 440.88 (100) [M – 1]+,
442.66 (41) [M + 1]+. C19H12ClN5O4S (441.85): calcd. C 51.65, H
2.74, N 15.85; found C 51.27, H 3.03, N 15.49.
General Procedure for the Preparation of Thiophenes by the Dehy-
drogenation of Dihydrothiophenes: A suspension of dihydrothio-
phene (2.0 mmol) and DDQ (2.4 mmol, 0.545 g) in acetonitrile
(10 mL) was stirred at 35–40 °C for about 2–4 h. The resulting pre-
cipitate was filtered and washed with acetonitrile to give to give the
pure products 3a–3e.
CCDC-727666 (for 1e), -727669 (for 2c), -727672 (for 2f), -727667
(for 2i), -727670 (for 2j), -727671 (for 2l) and -727668 (for 3e) con-
tain the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
3a: White solid, 93%, m.p. Ͼ250 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.26 (s, 1 H, NH), 9.19 (s, 1 H, NH), 8.20 (s, 2 H,
NH2), 7.60 (d, J = 8.4 Hz, 2 H, ArH), 7.50–7.46 (m, 4 H, ArH),
7.30 (t, J = 7.2 Hz, 2 H, ArH), 7.07 (t, J = 7.2 Hz, 1 H, ArH) ppm.
13C NMR (150 MHz, [D6]DMSO): δ = 167.6, 162.4, 150.5, 145.2,
137.9, 134.7, 131.9, 131.5, 129.3, 129.2, 124.2, 120.1, 115.2, 112.1,
Acknowledgments
This work was financially supported by the National Natural Sci-
ence Foundation of China (Grant No. 20672091).
89.1 ppm. IR (KBr): ν = 3374, 3295, 3203, 2216, 1691, 1632, 1597,
˜
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1557, 1526, 1501, 1472, 1443, 1413, 1304, 1256, 1225, 1152, 1088,
1014, 890, 833, 753 cm–1. MS: m/z (%) = 395.67 (100) [M – 1]+,
397.57 (46) [M + 1]+. C19H13ClN4O2S (396.85): calcd. C 57.50, H
3.30, N 14.12; found C 57.42, H 3.68, N 13.75.
3b: White solid, 95%, m.p. Ͼ250 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.28 (s, 1 H, NH), 9.19 (s, 1 H, NH), 8.15 (s, 2 H,
NH2), 7.58 (d, J = 8.4 Hz, 2 H, ArH), 7.51–7.47 (m, 4 H, ArH),
7.34 (d, J = 9.0 Hz, 2 H, ArH) ppm. 13C NMR (150 MHz, [D6]-
DMSO): δ = 167.6, 162.4, 150.6, 145.4, 136.9, 134.6, 131.9, 131.5,
129.2, 127.9, 121.8, 115.2, 111.9, 89.1 ppm. IR (KBr): ν = 3452,
˜
3311, 3215, 2214, 1729, 1637, 1551, 1501, 1478, 1403, 1311, 1264,
1216, 1094, 1011, 820, 743 cm–1. MS: m/z (%) = 429.71 (100) [M –
1]+, 431.44 (70) [M + 1+]. C19H12Cl2N4O2S (431.30): calcd. C
52.91, H 2.80, N 12.99; found C 52.76, H 3.28, N 12.66.
3c: Light-yellow solid, 94%, m.p. Ͼ250 °C. 1H NMR (600 MHz,
[D6]DMSO): δ = 10.16 (s, 1 H, NH), 9.05 (s, 1 H, NH), 8.13 (s, 2
H, NH2), 7.72 (d, J = 8.4 Hz, 2 H, ArH), 7.41 (d, J = 8.4 Hz, 2 H,
ArH), 7.33 (d, J = 8.4 Hz, 2 H, ArH), 7.10 (d, J = 8.4 Hz, 2 H,
ArH), 2.24 (s, 3 H, CH3) ppm. 13C NMR (150 MHz, [D6]DMSO):
δ = 167.5, 162.4, 150.4, 145.2, 135.3, 133.2, 132.3, 131.8, 129.7,
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123.3, 120.2, 115.2, 112.0, 88.9, 20.8 ppm. IR (KBr): ν = 3458,
˜
3317, 3213, 2213, 1702, 1628, 1594, 1550, 1521, 1472, 1408, 1306,
1261, 1216, 1169, 811, 757 cm–1. MS: m/z (%) = 453.58 (100) [M –
1]+, 455.50 (98) [M + 1]+. C20H15BrN4O2S (455.33): calcd. C 52.76,
H 3.32, N 12.30; found C 52.55, H 3.51, N 12.04.
3d: White solid, 95%, m.p. Ͼ250 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.27 (s, 1 H, NH), 9.23 (s, 1 H, NH), 8.19 (s, 2 H,
NH2), 7.73 (d, J = 8.4 Hz, 2 H, ArH), 7.47 (d, J = 8.4 Hz, 2 H,
ArH), 7.4.2 (d, J = 8.4 Hz, 2 H, ArH), 7.30 (t, J = 7.8 Hz, 2 H,
ArH), 7.07 (t, J = 7.8 Hz, 1 H, ArH) ppm. 13C NMR (150 MHz,
[D6]DMSO): δ = 167.6, 162.4, 150.5, 145.3, 137.9, 132.3, 132.2,
131.8, 129.3, 124.2, 123.4, 120.2, 115.2, 112.0, 89.0 ppm. IR (KBr):
[10] a) V. S. Matiychuk, R. B. Lesyk, M. O. Obushak, A. Gzella,
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˜
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1500, 1472, 1443, 1413, 1386, 1305, 1256, 1226, 1153, 1085, 1011,
890, 833, 753 cm–1. MS: m/z (%) = 439.66 (100) [M – 1]+, 441.58
(98) [M + 1]+. C19H13BrN4O2S (441.30): calcd. C 51.71, H 2.97, N
12.70; found C 51.64, H 3.22, N 12.48.
3e: Yellow solid, 90%, m.p. 242–243 °C. 1H NMR (600 MHz, [D6]-
DMSO): δ = 10.22 (s, 1 H, NH), 9.90 (s, 1 H, NH), 8.34–8.32 (m,
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Eur. J. Org. Chem. 2009, 5247–5254
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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Received: July 26, 2009
Published Online: September 15, 2009
5254
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5247–5254