A simple synthesis of alkyl 2-aminobenzo[ b ]thiophene-3-carboxylates via an unexpected dehydrogenation of alkyl 2-amino-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxylates

Article abstract of DOI:10.1055/s-0034-1379475

A simple method for the preparation of alkyl 2-aminobenzo[b]thiophene-3-carboxylates is described. Alkyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylates, generated from the Gewald three-component reaction between cyclohexanones, alkyl cyanoacet

Full text of DOI:10.1055/s-0034-1379475

2918▌
LETTER
lAetteSr imple Synthesis of Alkyl 2-Aminobenzo[b]thiophene-3-carboxylates via an
Unexpected Dehydrogenation of Alkyl 2-Amino-4,5,6,7-tetrahydrobenzo[b]-
thiophene-3-carboxylates
Alkyl 2-Aminobenzo[b]thiophene-3-carboxylates
Mehdi Adib,*a Maryam Bayanati,a Mehdi Soheilizad,a Helia Janatian Ghazvini,a Mahmood Tajbakhsh,b
Massoud Amanlouc
a
School of Chemistry, 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
Department of Organic Chemistry, Faculty of Chemistry, Mazandaran University, Babolsar, Iran
c
Pharmaceutical Sciences Research Center and Department of Medicinal Chemistry, Tehran University of Medical Sciences, Tehran, Iran
Received: 25.08.2014; Accepted: 21.09.2014
O
O
Abstract: A simple method for the preparation of alkyl 2-amino-
benzo[b]thiophene-3-carboxylates is described. Alkyl 2-amino-
N
HO
O
4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylates,
generated
OH
N
from the Gewald three-component reaction between cyclohex-
anones, alkyl cyanoacetates and sulfur, undergo dehydrogenation in
benzonitrile under an air atmosphere to afford alkyl 2-aminoben-
zo[b]thiophene-3-carboxylates in good to excellent yields.
S
NH2
HO
O
Me
2
S
1
Key words: 2-aminobenzo[b]thiophene-3-carboxylates, Gewald
reaction, cyclohexanones, cyanoacetates, benzonitrile, dehydroge-
nation, heterocycles
O
N
OMe
S
HO
3
Benzo[b]thiophenes are an important class of heterocyclic
compounds with diverse applications in biology,1 phar-
macy,2 material sciences,3 and catalysis.4 It has been re-
ported that benzo[b]thiophene derivatives have exhibited
a wide range of biological properties, such as antifungal,5
anti-inflammatory,6 antiestrogen,7 anticancer8 analgesic,9
pesticide10 and kinases inhibitory activity.11 Along with
various biological activities, these sulfur-containing het-
erocycles have found many uses in medicinal industries.
For example, zileuton (1), raloxifene (2) and arzoxifene
(3) (Figure 1) are commercially available drugs with ben-
zo[b]thiophene core structure.12–14
Figure 1 Examples of drugs having benzo[b]thiophene core struc-
ture
In continuation of our previous studies on the develop-
ment of efficient methods for the synthesis of biologically
active heterocyclic compounds,22 we wish to report a sim-
ple and novel method for the preparation of alkyl ABTCs.
At the beginning of study we found that a mixture of cy-
clohexanone (4a), ethyl cyanoacetate (5b), and elemental
sulfur in the presence of morpholine at 75 °C underwent
the Gewald reaction to give ethyl ATHBTC 6b. This Ge-
wald 2-aminothiophene was isolated and treated with ben-
zonitrile in the presence of an equivalent amount of a base
such as K2CO3 or NaOH to give 2-phenyl-5,6,7,8-tetrahy-
drobenzothieno[2,3-d]pyrimidin-4(3H)-one (8). TLC
monitoring of the reaction mixture exhibited formation of
a new product, which was purified. Identification of its
structure by NMR spectroscopy serendipitously revealed
that it was the fully dehydrogenated–aromatized product
7b, not the expected condensation–cyclization product 8
(Scheme 1).
Due to the their wide range of applications, benzo[b]thio-
phenes have attracted much synthetic attention.15,16 Sever-
al new synthetic approaches to these heterocycles have
been introduced in recent years,17 however, only a few
methods have been reported for the preparation of 2-ami-
nobenzo[b]thiophene-3-carboxylates (ABTCs) via oxida-
tion of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carboxylates (ATHBTCs). These dehydrogenations/oxi-
dations have been performed by the use of Pd/C, DDQ, or
NBS/AIBN.18–21 The ATHBTCs are readily accessible by
the Gewald reaction of cyclohexanones, cyanoacetates
and sulfur.
In order to evaluate the influence of time and temperature
in this reaction, treatment of 6b with an excess of benzo-
nitrile (1 mL for 0.5 mmol of 6b) under an air atmosphere
was investigated and the progress of the reactions was
monitored by TLC (Table 1). Among all the conditions
tested, a reaction time of 24 hours and a temperature of
200 °C were the optimal conditions in which 7b was ob-
tained in 93% yield (Table 1, entry 7).
SYNLETT 2014, 25, 2918–2922
Advanced online publication: 14.11.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1379475; Art ID: st-2014-d0713-l
© Georg Thieme Verlag Stuttgart · New York

LETTER
Alkyl 2-Aminobenzo[b]thiophene-3-carboxylates
2919
CO2Et
NH2
Table 2 Effect of Different Conditions on Dehydrogenation of 6b
O
+
CO2Et
morpholine
PhCN
+
S8
Entry
Conditions
Time (h) Yield of 7b (%)
75 °C, 1 h
solvent-free
base, heat
CN
S
6b
4a
5b
1
2
3
4
5
PhCN + Ar
air
24
24
24
24
6
no reaction
O
CO2Et
NH2
complex reaction mixture
NH
O2
complex reaction mixture
N
S
S
PhCN + air
PhCN + O2
93
94
7b
8, was not observed
Scheme 1 Synthesis of 6b followed by treatment with benzonitrile
In order to explore the effect of the nitrile type on the re-
action, we used different benzonitrile derivatives for the
dehydrogenation of 6b. All the reactions were carried out
at 200 °C for 24 hours. The reaction did not proceed well
by the use of benzonitrile derivative with electron-with-
drawing nitro group and the reaction yield was 40% (Ta-
ble 3, entry 5). The best results were obtained with
electron-donating methoxy group (Table 3, entry 4). Ben-
zonitrile was selected because of its high yield of the de-
hydrogenated product (Table 3, entry 1), easier
availability and lowest price. We also performed the reac-
tion using nitrobenzene instead of benzonitrile under sim-
ilar conditions; however, the dehydrogenated product 7b
was not detected by TLC (Table 3, entry 6).
Table 1 Effect of Different Reaction Times and Temperatures on
Dehydrogenation of 6b in PhCN/Air
Entry
Time (h)
Temp (°C)
Yield (%) of 7b
1
2
3
4
5
6
7
8
2
5
100
100
150
150
150
200
200
200
5
15
26
35
67
62
93
93
5
10
24
10
24
30
Table 3 Effect of Different Benzonitriles on Dehydrogenation of 6b
Entry
Conditions
Yield of 7b (%)
To find out the effective factors for the dehydrogenation
of 6b, some other experiments were also designed and the
reaction was carried out under different conditions. All
the reactions were performed at 200 °C and the progress
of the reactions was monitored by TLC. On carrying out
the reaction in benzonitrile under an argon atmosphere,
the TLC of the reaction mixture did not exhibit formation
of the dehydrogenated product (Table 2, entry 1). When
the reaction was performed in the absence of benzonitrile
under an air or oxygen atmosphere, complex mixtures in
addition to some starting material were obtained after 24
hours (Table 2, entries 2 and 3). However, performing the
reaction in benzonitrile under an air atmosphere led to the
dehydrogenation of 6b to 7b in 93% yield after 24 hours
(Table 2, entry 4), whereas under an oxygen atmosphere,
instead of air, the reaction proceeded smoothly with 94%
yield after six hours (Table 2, entry 5). The results are
summarized in Table 2.
1
2
3
4
5
6
PhCN + air
93
80
85
95
40
–
4-ClC6H4CN + air
3-MeC6H4CN + air
4-MeOC6H4CN + air
4-O2NC6H4CN + air
PhNO2 + air
After optimization of the reaction conditions, a series of
alkyl ATHBTCs 6 were prepared which subsequently de-
hydrogenated to the corresponding alkyl ABTCs 7. Thus,
a mixture of a cyclohexanone 4, an alkyl cyanoacetate 5,
and elemental sulfur in the presence of morpholine at 75
°C underwent the Gewald reaction to afford 6. Then, a
solution of the isolated product 6 in benzonitrile was heat-
ed under an air atmosphere at 200 °C for 24 hours to pro-
X
X
X
CO2R
NH2
CO2R
NH2
O
CO2R
PhCN, air
morpholine
Y
S8
+
Y
+
200 °C, 24 h
75 °C, 1 h
solvent-free
CN
S
S
Y
4
5
6
7
X = H, Me, CO2Et
Y = H, Me, Ph
R = Me, Et
Scheme 2 Synthesis of alkyl 2-aminobenzo[b]thiophene-3-carboxylates 7
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2918–2922

2920
M. Adib et al.
LETTER
1
duce the corresponding alkyl ABTCs 7a–j (Scheme 2). none, ethyl cyanoacetate and sulfur. The H NMR spec-
TLC and NMR spectroscopic analysis of the reaction mix- trum of 7b showed the disappearance of the
tures clearly indicated the formation of 7 in good to excel- distinguishable signals for eight protons related to the four
lent yields.23 The results are summarized in Table 4.
methylenes of the cyclohexanone residue in the expected
range of δ = 1.70–3.00 ppm of the spectrum and appear-
ance of the attributable signals to four aromatic protons in
the range of δ = 7.00–8.20 ppm with appropriate chemical
shifts and coupling constants, which confirmed the dehy-
drogenation and aromatization. In addition, the 1H NMR
spectrum exhibited triplet and quartet signals (at δ = 1.49
and 4.44 ppm; J = 7.2 Hz) for the ethyl group, as well as
a broad signal at δ = 6.56 ppm arising from NH2 group. In
the 1H-decoupled 13C NMR spectrum of 7b four apparent
signals of the four methylenes in the range of δ = 22–26
ppm disappeared and four noticeable signals due to the ar-
omatic CHs of the phenylene moiety were seen at δ =
121.3, 122.4, 122.5 and 125.5 ppm, along with other four
signals due to the quaternary carbons (at δ = 99.7, 128.8,
137.4 and 164.4 ppm) of the thiophene ring. Characteris-
tic signals at δ = 14.6, 59.9 ppm arising from the ethyl
group as well as a deshielded resonance at δ = 166.4 ppm
(for carbonyl group) were observed in agreement with the
proposed structure.23
Table 4 Synthesis of Alkyl 2-Aminobenzo[b]thiophene-3-carboxyl-
ates 7a–j
Entry X
Y
H
H
R
Alkyl ABTC (7)
Yield Mp °C
(%)a (Lit.)
CO2Me
126–128
91
a
H
Me
Et
(129)20
NH2
S
S
CO2Et
116
93
b
c
H
H
H
(107–108)21
NH2
CO2Me
Me Me
Me Et
90 118–120
NH2
S
S
CO2Et
127–128
93
d
(126–128)19
NH2
A mechanistic rationalization for this dehydrogenation–
aromatization is provided in Scheme 3. At first, reaction
between benzonitrile and O2 may form a dioxazete inter-
mediate 9, which can undergo an electrocyclic ring open-
ing to give the electron-deficient acyl nitroso intermediate
10. The acyl nitroso intermediate can dehydrogenize tet-
rahydrobenzo[b]thiophene 6 through the six-membered
six-electron transition states TS1 and TS2 to form alkyl 2-
aminobenzo[b]thiophene-3-carboxylates 7. In this trans-
formation the acyl nitroso intermediate reduces to benzo-
hydroxamic acid 11. Abstraction of pairs of hydrogens
from adjacent carbons of the carbocyclic ring may be a
concerted process. Similar structures have been proposed
for the transition states in the nitroso-ene reactions.24 GC–
MS analysis of the reaction mixture revealed the presence
of benzohydroxamic acid 11, which can strengthen the
proposed mechanism.
CO2Et
CO2Me
e
CO2Et
H
Me
88 oil
NH2
S
CO2Et
CO2Et
NH2
f
CO2Et
Me
H
H
H
Et
90 oil
85 oil
88 oil18
S
S
S
CO2Me
NH2
g
h
Me
Et
CO2Et
NH2
Me
In summary, we have developed a simple and efficient
protocol for the synthesis of alkyl 2-aminobenzo[b]thio-
phene-3-carboxylates via dehydrogenation of alkyl 2-
amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxyl-
ates with benzonitrile under an air atmosphere. Good to
excellent yields of the products, metal-free dehydrogena-
tion without any need for normal oxidants and use of sim-
ple starting materials are the main advantages of this
method.
CO2Me
i
H
H
Ph Me
Ph Et
93 145–146
95 oil
Ph
Ph
NH2
S
S
CO2Et
j
NH2
a Isolated yields.
Acknowledgment
The structures of the isolated products were confirmed by
IR, 1H NMR and 13C NMR spectroscopy and mass spec-
trometry. The IR spectrum of 7b showed the stretching
bands for N–H and C=O functionalities at 3395, 3277,
3159 and 1641 cm–1. The mass spectrum of 7b displayed
the molecular ion (M+) peak at m/z = 221, which was four
units less than that of the Gewald product of cyclohexa-
This research was supported by the Research Council of the Univer-
sity of Tehran.
References and Notes
(1) Gai, Z.; Yu, B.; Wang, X.; Deng, Z.; Xu, P. Microbiology
2008, 154, 3804.
Synlett 2014, 25, 2918–2922
© Georg Thieme Verlag Stuttgart · New York

LETTER
Alkyl 2-Aminobenzo[b]thiophene-3-carboxylates
2921
O
O
O
N
O
O
N
O
Ph
Ph
N
Ph
9
10
H
O
Ph
N
CO2R
NH2
CO2R
NH2
CO2R
NH2
OH
11
O
Ph
N
H
H
O
CO2R
NH2
10
10
7
S
H
S
S
11
Ph
N
H
S
O
6
TS1
TS2
O
Scheme 3 Proposed mechanism for the dehydrogenation of 4,5,6,7-tetrahydrobenzo[b]thiophenes 6 to benzo[b]thiophenes 7
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Aminobenzo[b]thiophene-3-carboxylates 7a–j,
Exemplified with 7a: A mixture of cyclohexanone (0.196 g,
2.0 mmol), methyl cyanoacetate (0.198 g, 2.0 mmol),
elemental sulfur (0.064 g, 2.0 mmol) and morpholine (0.174
g, 2.0 mmol) was heated at 75 °C for 1 h. After nearly
complete conversion to the corresponding 2-
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aminothiophene, as was indicated by TLC monitoring, the
reaction mixture was cooled to r.t. and the solid residue was
recrystallized from EtOH to afford methyl 2-amino-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carboxylate (6a). Then a
solution of 6a (0.211 g, 1 mmol) in benzonitrile (2 mL) was
heated within a flask equipped with an air-filled balloon at
200 °C for 24 h in a silicone oil bath. Progress of the reaction
was monitored by TLC. After completion of the reaction, the
mixture was cooled to r.t. and the excess of benzonitrile was
removed under the reduced pressure. The crude product was
purified by column chromatography using n-hexane–EtOAc
(8:1) as eluent. The solvent was evaporated under the
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2918–2922

2922
M. Adib et al.
LETTER
reduced pressure and the residue was crystallized from n-
hexane–EtOAc (5:1) to afford the pure product 7a as pale
yellow crystals. Yield: 0.188 g, 91% (on the basis of 6a). IR
(KBr): 3395, 3280, 3167 (NH), 1647 (C=O) cm–1. 1H NMR
(500.1 MHz, CDCl3): δ = 3.97 (s, 3 H, Me), 6.55 (br s, 2 H,
NH2), 7.16 (td, J = 7.6, 1.2 Hz, 1 H, CH), 7.34 (td, J = 7.8,
1.2 Hz, 1 H, CH), 7.52 (d, J = 8.0 Hz, 1 H, CH), 8.10 (d, J =
8.0 Hz, 1 H, CH). 13C NMR (100.6 MHz, CDCl3): δ = 51.1
(OMe), 99.7 (CCO2), 121.4, 122.4, 122.5, 125.5 (4 × CH),
128.8, 137.3 (2 × C), 164.5 (SCN), 166.7 (C=O). MS: m/z
(%) = 207 (95) [M+], 175 (100). Anal. Calcd for C10H9NO2S
(207.25): C, 57.95; H, 4.38; N, 6.76. Found: C, 58.08; H,
4.42; N, 6.68. 7b: pale yellow crystals. Yield: 0.205 g (93%).
IR (KBr): 3395, 3277, 3159 (NH), 1641 (C=O) cm–1. 1H
NMR (400.1 MHz, CDCl3): δ = 1.49 (t, J = 7.2 Hz, 3 H, Me),
4.44 (q, J = 7.2 Hz, 2 H, CH2), 6.56 (br s, 2 H, NH2), 7.16 (td,
J = 7.6, 1.2 Hz, 1 H, CH), 7.34 (td, J = 7.8, 1.2 Hz, 1 H, CH),
7.52 (d, J = 7.8 Hz, 1 H, CH), 8.13 (d, J = 8.2 Hz, 1 H, CH).
13C NMR (100.6 MHz, CDCl3): δ = 14.6 (Et), 59.9 (OEt),
99.7 (CCO2), 121.3, 122.4, 122.5, 125.5 (4 × CH), 128.8,
137.4 (2 × C), 164.4 (SNC), 166.4 (C=O). MS: m/z (%) =
221 (83) [M+], 175 (100). Anal. Calcd for C11H11NO2S
(221.28): C, 59.71; H, 5.01; N, 6.33. Found: C, 59.69; H,
5.13; N, 6.27. 7c: pale yellow crystals. Yield: 0.199 g, 90%.
IR (KBr): 3411, 3298 (NH), 1650 (C=O) cm–1. 1H NMR
(400.1 MHz, CDCl3): δ = 2.41 (s, 3 H, Me), 3.96 (s, 3 H,
OMe), 6.50 (br s, 2 H, NH2), 7.15 (d, J = 8.4 Hz, 1 H, CH),
7.33 (br s, 1 H, CH), 7.97 (d, J = 8.4 Hz, 1 H, CH). 13C NMR
(100.6 MHz, CDCl3): δ = 21.2 (Me), 51.0 (OMe), 99.5
(CCO2), 121.4, 122.2, 126.8 (3 × CH), 129.0, 132.2, 134.7 (3
× C), 163.9 (CNS), 166.7 (C=O). MS: m/z (%) = 221 (72)
[M+], 189 (100). Anal. Calcd for C11H11NO2S (221.28): C,
59.71; H, 5.01; N, 6.33. Found: C, 59.86; H, 5.04; N, 6.30.
7d: pale yellow crystals. Yield: 0.211 g, 90%. IR (KBr):
3410, 3294 (NH), 1643 (C=O) cm–1. 1H NMR (400.1 MHz,
CDCl3): δ = 1.48 (t, J = 7.2 Hz, 3 H, Me), 2.41 (s, 3 H, Me),
4.43 (q, J = 7.2 Hz, 2 H, CH2), 6.48 (br s, 2 H, NH2), 7.15 (d,
J = 8.4 Hz, 1 H, CH), 7.33 (br s, 1 H, CH), 8.00 (d, J = 8.4
Hz, 1 H, CH). 13C NMR (100.6 MHz, CDCl3): δ = 14.6 (Et),
21.2 (Me), 59.9 (OEt), 99.6 (CCO2), 121.4, 122.2, 126.8 (3
× CH), 129.0, 132.1, 134.9 (3 × C), 163.8 (CNS), 166.3
(C=O). MS: m/z (%) = 235 (66) [M+], 189 (100). Anal. Calcd
for C12H13NO2S (235.31): C, 61.25; H, 5.57; N, 5.95. Found:
C, 61.24; H, 5.46; N, 5.91. 7e: yellow oil. Yield: 0.245 g,
88%. IR (KBr): 3426, 3320 (NH), 1713, 1674 (C=O) cm–1.
1H NMR (500.1 MHz, CDCl3): δ = 1.36 (t, J = 7.2 Hz, 3 H,
Et), 3.83 (s, 3 H, OMe), 4.34 (q, J = 7.2 Hz, 2 H, OEt), 6.35
(br s, 2 H, NH2), 7.18 (t, J = 7.6 Hz, 1 H, CH), 7.61 (dd, J =
7.6, 1.2 Hz, 1 H, CH), 7.62 (dd, J = 7.6, 1.2 Hz, 1 H, CH).
13C NMR (100.6 MHz, CDCl3): δ = 14.2 (Et), 51.0 (OMe),
60.9 (OEt), 101.0 (CCO2), 121.9, 124.0, 126.8 (3 × CH),
127.0, 130.4, 134.5 (3 × C), 163.3 (CNS), 165.8, 169.5 (2 ×
C=O). MS: m/z (%) = 279 (85) [M+], 175 (100). Anal. Calcd
for C13H13NO4S (279.32): C, 55.90; H, 4.69; N, 5.01. Found:
C, 55.78; H, 4.75; N, 4.84. 7f: yellow oil. Yield: 0.258 g,
88%. IR (KBr): 3428, 3322, 3179 (NH), 1714, 1670 (C=O)
cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 1.34 (t, J = 7.2 Hz,
3 H, Et), 1.35 (t, J = 7.2 Hz, 3 H, Et), 4.31 (q, J = 7.2 Hz, 2
H, OEt), 4.33 (q, J = 7.2 Hz, 2 H, OEt), 6.26 (br s, 2 H, NH2),
7.18 (t, J = 7.6 Hz, 1 H, CH), 7.61 (dd, J = 7.6, 1.2 Hz, 1 H,
CH), 7.64 (dd, J = 7.6, 1.2 Hz, 1 H, CH). 13C NMR (100.6
MHz, CDCl3): δ = 14.2, 14.2 (2 × Et), 60.4, 60.8 (2 × OEt),
99.9 (CCO2), 121.8, 124.1 (2 × CH), 126.9 (C), 127.0 (CH),
130.5, 134.9 (2 × C), 163.3 (CNS), 165.6, 169.3 (2 × C=O).
MS: m/z (%) = 293 (72) [M+], 175 (100). Anal. Calcd for
C14H15NO4S (293.34): C, 57.32; H, 5.15; N, 4.77. Found: C,
57.49; H, 5.26; N, 4.58. 7g: yellow oil. Yield: 0.188 g, 85%.
IR (KBr): 3391, 3286, 3171 (NH), 1647 (C=O) cm–1. 1H
NMR (400.1 MHz, CDCl3): δ = 2.51 (s, 3 H, Me), 3.92 (s, 3
H, Me), 6.10 (br s, 2 H, NH2), 7.09 (t, J = 7.6 Hz, 1 H, CH),
7.14 (d, J = 7.5 Hz, 1 H, CH), 7.38 (d, J = 7.5 Hz, 1 H, CH).
13C NMR (100.6 MHz, CDCl3): δ = 23.2 (Me), 50.9 (OMe),
101.8 (CCO2), 119.0, 122.6, 128.7 (3 × CH), 129.9, 132.8,
135.9 (3 × C), 162.2 (CNS), 166.2 (C=O). MS: m/z (%) =
221 (13) [M+], 64 (100). Anal. Calcd for C11H11NO2S
(221.28): C, 59.71; H, 5.01; N, 6.33. Found: C, 59.63; H,
4.90; N, 6.21. 7h: yellow oil. Yield: 0.200 g, 85%. IR (KBr):
3433, 3327 (NH), 1660 (C=O) cm–1. 1H NMR (500.1 MHz,
CDCl3): δ = 1.42 (t, J = 7.2 Hz, 3 H, Et), 2.54 (s, 3 H, Me),
4.40 (q, J = 7.2 Hz, 2 H, OEt), 6.11 (br s, 2 H, NH2), 7.09 (t,
J = 7.6 Hz, 1 H, CH), 7.14 (d, J = 7.6 Hz, 1 H, CH), 7.38 (d,
J = 7.6 Hz, 1 H, CH). 13C NMR (100.6 MHz, CDCl3): δ =
14.5 (2 × Et), 23.5 (Me), 60.3 (OEt), 102.2 (CCO2), 119.0,
122.6, 128.6 (3 ×× CH), 129.9, 131.8, 136.0 (3 × C), 162.1
(CNS), 166.0 (C=O). MS: m/z (%) = 235 (87) [M+], 189
(100). Anal. Calcd for C12H13NO2S (235.31): C, 61.25; H,
5.57; N, 5.95. Found: C, 61.40; H, 5.72; N, 5.76. 7i: pale
yellow crystals. Yield: 0.269 g, 95. IR (KBr): 3458, 3344
(NH), 1660 (C=O) cm–1. 1H NMR (500.1 MHz, CDCl3): δ =
3.40 (s, 3 H, OMe), 6.59 (br s, 2 H, NH2), 7.36 (tt, J = 7.6,
1.2 Hz, 1 H, CH), 7.47 (t, J = 7.6 Hz, 2 H, 2 × CH), 7.59 (dd,
J = 8.4, 1.6 Hz, 1 H, CH), 7.64 (dd, J = 7.6, 1.2 Hz, 2 H, 2 ×
CH), 7.76 (d, J = 1.6 Hz, 1 H, CH), 8.15 (d, J = 8.4 Hz, 1 H,
CH). 13C NMR (100.6 MHz, CDCl3): δ = 51.1 (OMe), 99.5
(CCO2), 119.7, 122.6, 124.8 (3 × CH), 126.9 (2 × CH), 127.0
(CH), 128.8 (2 × CH), 129.5, 135.7, 136.4, 140.9 (4 × C),
164.7 (SNC), 166.6 (C=O). MS: m/z (%) = 283 (99) [M+],
251 (100). Anal. Calcd for C16H13NO2S (283.35): C, 67.82;
H, 4.62; N, 4.94. Found: C, 67.83; H, 4.64; N, 4.92. 7j:
yellow oil. Yield: 0.282 g, 95%. IR (KBr): 3400, 3312 (NH),
1657 (C=O) cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 1.52
(t, J = 7.2 Hz, 3 H, Et), 4.48 (q, J = 7.2 Hz, 2 H, OEt), 6.66
(br s, 2 H, NH2), 7.37 (t, J = 7.6 Hz, 1 H, CH), 7.48 (t, J =
7.6 Hz, 2 H, 2 × CH), 7.61 (dd, J = 8.4, 1.6 Hz, 1 H, CH),
7.65 (dd, J = 7.6, 1.2 Hz, 2 H, 2 × CH), 7.76 (d, J = 1.6 Hz,
1 H, CH), 8.19 (d, J = 8.4 Hz, 1 H, CH). 13C NMR (100.6
MHz, CDCl3): δ = 14.6 (Me), 60.0 (OCH2), 99.6 (CCO2),
119.7, 122.7, 124.8 (3 × CH), 126.9 (2 × CH), 127.0 (CH),
128.8 (2 × CH), 129.6, 135.5, 136.6, 141.0 (4 × C), 164.7
(SCN), 166.3 (C=O). MS: m/z (%) = 297 (51) [M+], 57
(100). Anal. Calcd for C17H15NO2S (297.38): C, 68.66; H,
5.08; N, 4.71. Found: C, 68.79; H, 5.23; N, 4.57.
(24) (a) Fokin, A. A.; Yurchenko, A. G.; Rodionov, V. N.;
Gunchenko, P. A.; Yurchenko, R. I.; Reichenberg, A.;
Wiesner, J.; Hintz, M.; Jomaa, H.; Schreiner, P. R. Org. Lett.
2007, 9, 4379. (b) Adam, W.; Krebs, O. Chem. Rev. 2003,
103, 4131.
Synlett 2014, 25, 2918–2922
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