One-pot regioselective synthesis of 3-benzylthiazolo[3,2-a]indoles by sequential sonogashira coupling followed by triethylamine-induced cyclization

Article abstract of DOI:10.1055/s-0030-1259971

A number of 2-(prop-2-ynylthio)-1H-indoles have been utilized for the synthesis of 3-benzylthiazolo[3,2-a]indoles by Sonogashira acetylide-coupling followed by triethylamine-induced regioselective cyclization in a one-pot operation. The cyclization is dependent on the nature of the substituents on the phenyl ring of the substrates. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1259971

PAPER
1413
One-Pot Regioselective Synthesis of 3-Benzylthiazolo[3,2-a]indoles by
Sequential Sonogashira Coupling Followed by Triethylamine-Induced
Cyclization
R
egioselective Syn
.
thesis of 3-B
C
enzylthiazolo[3,
.
2-
a
]indoles Majumdar,*1 Sanjay Nath
Department of Chemistry, University of Kalyani, Kalyani 741235, W. B., India
Fax +91(33)25828282; E-mail: kcm_ku@yahoo.co.in
Received 31 January 2011; revised 21 February 2011
of molecules. Heterocyclization could be effected from
these conjugated acetylenic compounds either by transi-
tion-metal-mediated,12 or by base-mediated,13 or by iodo-
cyclization.14 We have recently reported the synthesis of
Abstract: A number of 2-(prop-2-ynylthio)-1H-indoles have been
utilized for the synthesis of 3-benzylthiazolo[3,2-a]indoles by
Sonogashira acetylide-coupling followed by triethylamine-induced
regioselective cyclization in a one-pot operation. The cyclization is
dependent on the nature of the substituents on the phenyl ring of the various heterocyclic systems via Sonogashira cross cou-
pling followed by copper(I) iodide15 or gold-catalyzed16
substrates.
cyclization. We undertook a study for the synthesis of
thiazolo[3,2-a]indole derivatives, a structural core worthy
of evaluation for biological properties by combining
Sonogashira acetylide coupling followed by triethylamine-
induced annulation reaction in a one-pot operation. The
results are reported here.
Although a method9 is available for the synthesis of thia-
zolo[3,2-a]indole, a literature survey showed no reference
concerning the use of a Pd/Cu-catalyzed preparation of
this system.
Key words: Sonogashira coupling, palladium catalyst, base-
promoted cyclization, aryl iodide, thiazoloindole
Thiazoles are useful heterocycles and building blocks and
a prominent structural moiety of compounds relevant to
treatment of cancer, bacterial, fungal, and viral infec-
tions,2 and are known to exhibit pharmacological activi-
ties.3 Because of their wide range of important biological
activities, they serve as attractive targets to the synthetic
organic chemists. Thiazoles fused to different heterocy-
clic compounds are of importance not only as medicinal
agents but also as organic functional materials such as
fluorescent dyes.4 Several of such heterocycle-fused thia-
zole derivatives have been prepared by Sonogashira
cross-coupling methodology.5
The required precursors 2-(prop-2-ynylthio)-1H-indoles
1a–e were synthesized according to the published proce-
dure.10c When Sonogashira coupling reaction were per-
formed on 2-(prop-2-ynylthio)-1H-indoles 1a–e with aryl
iodide 2a in the presence of bis(triphenylphosphine)palla-
dium(II) chloride as catalyst, cuprous iodide as co-cata-
lyst, and base triethylamine in anhydrous N,N-
dimethylformamide at room temperature for three hours,
a single compound was obtained as detected by TLC. The
new compound was identified from its spectral data as the
expected Sonogashira coupling product 3a. The com-
pound 3a was heated at 90 °C under basic condition for
four hours to yield the desired 3-(4-acetylbenzyl)thiazo-
lo[3,2-a]indole (4a) in 82% yield (Scheme 1). The prod-
uct 4a was identified from its spectral data. The 1H NMR
spectrum exhibits one singlet for two protons at d = 4.49,
which correspond to benzylic protons. It also reveals one
singlet at d = 5.97 and another one singlet at d = 6.57,
which correspond to the protons of thiazole and pyrrole
ring, respectively. The 13C NMR spectrum and HRMS
analysis also support the proposed structure. It is relevant
to mention here that the substrate 1a at 90 °C readily un-
dergoes thio-Claisen rearrangement to give the product
5.17 On the basis of this the substrate 3a when heated at
90 °C is also expected to provide compounds 6 and/or 7.
Notably we did not obtain any 6 or 7 at all.
Moreover, indole nucleus is a prominent structural sub-
unit present in numerous natural products and synthetic
compounds with vital medicinal value.6 The assembly of
functionalized indole and condensed indole derivatives
has captured the attention of synthetic chemists for de-
cades due to their pharmacological activities. Furo[3,2-
b]indoles show analgestic and anti-inflammatory activi-
ty.7 Thienoindole derivatives are potentially biologically
active.8 Several condensed indole derivatives including
thiazoloindole derivatives can act as 5HT4 receptor antag-
onists.9 Considering the potent bioactivities of com-
pounds possessing a thiazoloindole core, the development
of a new strategy to synthesize efficiently thiazolo[3,2-
a]indole derivatives has attracted our attention. Addition-
al interest is derived from our long-standing efforts in the
synthesis of indole annulated heterocyclic compounds.10
Palladium/copper-catalyzed cross-coupling reaction of
terminal acetylene with sp2-C halides, that is, Sonogashira
coupling11 provides a useful method for synthesizing con-
jugated acetylenic compounds, which are important class
To optimize the cycloisomerization reaction a series of
experiments were performed on the compound 3a under
different conditions where sequential changes were made
to the base, solvent, and temperature (Table 1). It was
SYNTHESIS 2011, No. 9, pp 1413–1418
Advanced online publication: 24.03.2011
DOI: 10.1055/s-0030-1259971; Art ID: Z16311SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
1
1

1414
K. C. Majumdar, S. Nath
PAPER
COMe
X
S
N
H
6
I
COMe
X
Y
and/or
(ii)
(i)
N
H
S
+
N
S
H
1a
Z
2a X = H
MeOC
Y = H
3a
N
S
Z = COMe
Δ
7
H
N
S
N
S
H
5
4a COMe
Scheme 1 Reagents and conditions: (i) Pd(PPh3)2Cl2 (3 mol%), CuI (3 mol%), Et3N, DMF, r.t., 3 h (ii) Et3N, DMF, 90 °C, 4 h.
found that using triethylamine as a base in N,N-dimethyl- Substituents on the phenyl ring of the substrate 3 play a vi-
formamide at 90 °C for four hours (Table 1, entry 2) is tal role in this cycloisomerization reaction. It was found
suitable for running the reaction to afford the product 4a that the presence of electron-withdrawing groups such as
in 82% yield. Use of triethylamine in acetonitrile was COMe, NO2, CO2Et on the phenyl ring of the substrate 3
found to be effective, but yield of the cyclized product is essential for successful cycloisomerization. Aryl io-
was low (35%). Changing the base to potassium acetate or dides without electron-withdrawing substituents undergo
potassium carbonate in N,N-dimethylformamide or aceto- Sonogashira coupling readily but triethylamine-induced
nitrile was found to be ineffective and the product forma- cyclization does not occur even after long heating at ele-
tion did not occur at all. Use of potassium tert-butoxide vated temperature. The absence of at least one electron-
was effective but the yield of the product is low (15%). withdrawing substituents on the phenyl ring of the sub-
Temperature plays an important role in the reaction. strate 3 inhibits the triethylamine-induced cyclization
When the reaction is performed at 60 °C, it did not pro-
Table 1 Optimization of Base-Induced Cycloisomerization Reac-
tion of 3a
ceed at all. However, with increasing the temperature the
reaction proceeds slowly and it is optimum when the tem-
perature reaches to 90 °C. Further increase in temperature
decreases the yield of the product due to decomposition of
the cyclized product. The optimization experiments are
summarized in Table 1.
Entry
Solvent
DMF
Base
Temp (°C) Yield (%)
1
2
Et3N
60
90
n.r.a
82
DMF
Et3N
The reaction involves two-steps, a Sonogashira cross cou-
pling followed by base-induced cyclization. However, the
reaction can be conducted in a one-pot operation. The
one-pot reaction was achieved by Sonogashira coupling
reaction of the compound 1a with aryl iodide 2a at room
temperature for three hours to give 3a using the same cat-
alytic combination as mentioned before followed by heat-
ing the reaction mixture at 90 °C for four hours to afford
the desired cyclic product 4a in 80% yield (Table 2, entry
2). Other products 4b and 4d–l were prepared similarly.
Our attempts to achieve the same results by performing
the two steps of the same reaction in one pot at 90 °C re-
sulted in the formation of an inseparable complex mixture
of products.
3
MeCN
MeCN
DMF
Et3N
90
35
4
K2CO3
K2CO3
KOAc
KOAc
t-BuOK
t-BuOK
Et3N
90
n.r.a
n.r.a
n.r.a
n.r.a
20
5
90
6
DMF
90
7
MeCN
DMF
90
8
90
9
MeCN
DMF
90
15
10
>120
dec.b
a No reaction.
b Decomposition.
Synthesis 2011, No. 9, 1413–1418 © Thieme Stuttgart · New York

PAPER
Synthesis of 3-Benzylthiazolo[3,2-a]indoles
1415
(Table 2, entries 14, 15). However, for the substrate 4-io- entry 14) or without substitution (Table 2, entry 15) cy-
donitrobenzene (2c) (Table 2, entries 5, 6) and 3-chloro- clization does not occur. Further, for 4-nitro- (Table 2, en-
4-iodonitrobenzene (2e) (Table 2, entries 12, 13), both tries 5, 6) and 2-chloro-4-nitro-substituted (Table 2,
Sonogashira coupling as well as cyclization occur at room entries 12, 13) aryl iodides cyclization occur at room tem-
temperature in one-step to give the products 4d,e and 4k,l, perature. In the light of these observations, a plausible ra-
respectively. Intermediate Sonogashira coupling products tionalization for the formation of the products 4 may be
are not isolable in these cases. These results are summa- outlined18 (Scheme 2). Abstraction of the NH proton of
rized in Table 2. The products 4g–l are unstable and found the indole moiety by triethylamine may generate the anion
to decompose at room temperature while recording their 8. The latter may then undergo regioselective anionic 5-
NMR spectra.
exo-trig cyclization to form anionic thiazolo intermediate
9, which upon capture of a proton may furnish 10. Subse-
quent [1,3] proton shift in the presence of triethylamine
may furnish the desired 3-benzylthiazolo[3,2-a]indole 4.
The presence of an electron-withdrawing group on the
phenyl ring stabilizes the anionic intermediate 9 and,
therefore, cyclization may occur smoothly. For 4-nitro-
aryl iodide (2c) and 2-chloro-4-nitroaryl iodide (2e), the
intermediate 9 derives more stability due to the presence
It is found that the cycloisomerization process does not re-
quire any metal catalysis and that triethylamine used as
cosolvent as well as base was the sole reagent involved in
the heteroannulation reaction. Moreover, the presence of
an electron-withdrawing group such as COMe, NO2,
CO2Et on the aryl iodide is essential for the cycloisomer-
ization. For aryl iodides with chloro substitution (Table 2,
Table 2 Summarized Results of the Heteroannulation Reactiona
R3
R2
R3
R2
N
S
I
R3
R1
X
N
H
S
(ii)
(i)
+
R1
X
R2
N
S
Y
H
R1
1a–e
Z
Y
Z
X
2a–g
Z
Y
3a–n
4a–l
Entry
1
Substrates
1a/2a
1a/2a
1b/2a
1a/2b
1a/2c
1b/2c
1a/2d
1c/2d
1d/2d
1e/2d
1e/2b
1a/2e
1b/2e
1a/2f
R1
H
R2
R3
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
X
H
H
H
H
H
H
H
H
H
H
H
Cl
Cl
H
H
Y
Z
Product/Yield (%) Product/Yield (%)
H
H
H
H
H
H
H
H
Me
Cl
Cl
H
H
H
H
H
COMe
COMe
COMe
CO2Et
NO2
NO2
H
3a, 80
4a, 82
4a, 80
4b, 78
4c, 82
4d, 85
4e, 75
4f, 80
4g, 60d
4h, 65d
4i, 70d
4j, 80d
4k, 75d
4l, 73d
n.r.e
b
2
H
H
–
b
3
Me
H
H
–
4
H
3c, 85
c
5
H
H
–
c
6
Me
H
H
–
b
7
NO2
NO2
NO2
NO2
H
–
b
8
H
H
–
b
9
Me
Me
Me
H
H
–
b
10
11
12
13
14
15
H
–
b
CO2Et
NO2
NO2
Cl
–
c
H
–
c
Me
H
H
–
H
3m, 73
3n, 75
1a/2g
H
H
H
n.r.e
a Reaction conditions: (i) Pd(PPh3)2Cl2 (3 mol%), CuI (3 mol%), Et3N, DMF, r.t., 3 h; (ii) Et3N, DMF, 90 °C, 4 h.
b Product was not isolated, one-pot reaction was performed.
c Product could not be isolated, cyclization occurs at r.t.
d Products were isolated in pure form by column chromatography, but decomposes at r.t. while recording the NMR spectra.
e No reaction.
Synthesis 2011, No. 9, 1413–1418 © Thieme Stuttgart · New York

1416
K. C. Majumdar, S. Nath
PAPER
the column with EtOAc–PE (8:92) afforded the product 3a as a vis-
cous liquid; yield: 195 mg (80%).
IR (KBr): 1673, 2215, 3338 cm–1.
of nitro group at para position, which exerts more elec-
tron-withdrawing effect. Therefore, the cycloisomeriza-
tion is facile and occurs smoothly at room temperature.
1H NMR (400 MHz, CDCl3): d = 2.58 (s, 3 H, COCH3), 3.75 (s, 2
H, SCH2), 6.81 (s, 1 H, ArH), 7.12 (t, J = 7.6 Hz, 1 H, ArH), 7.22–
7.28 (m, 1 H, ArH), 7.32 (d, J = 8.0 Hz, 1 H, ArH), 7.40 (d, J = 7.2
Hz, 2 H, ArH), 7.59 (d, J = 7.6 Hz, 1 H, ArH), 7.87 (d, J = 7.2 Hz,
2 H, ArH), 8.39 (br s, 1 H, NH).
Et3N
N
N
S
S
N
S
H
Et3NH
Et3NH
X
MS: m/z for C19H15NOS = 306 [M+ + H].
3c
3
8
X
9
X
Yield: 228 mg (85%); colorless solid; mp 105 °C.
Et3NH
Et3N
IR (KBr): 1702, 2218, 3350 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.39 (t, J = 7.2 Hz, 3 H, CH2CH3),
3.74 (s, 2 H, SCH2), 4.37 (q, J = 7.2 Hz, 2 H, CH2CH3), 6.81 (d,
J = 1.6 Hz, 1 H, ArH), 7.12 (t, J = 7.6 Hz, 1 H, ArH), 7.23 (dq,
J = 6.8, 0.8 Hz, 1 H, ArH), 7.32 (d, J = 8.0 Hz, 1 H, ArH), 7.38 (d,
J = 8.0 Hz, 2 H, ArH), 7.59 (d, J = 8.0 Hz, 1 H, ArH), 7.96 (d,
J = 8.4 Hz, 2 H, ArH), 8.37 (br s, 1 H, NH).
Et3N
N
Et3NH
S
N
N
S
S
Et3N
H
MS: m/z for C20H17NO2S = 336 [M+ + H].
Et3NH
X
X
X
3m
4
11
10
Yield: 174 mg (73%); colorless solid; mp 95 °C.
IR (KBr): 2219, 3348 cm–1.
Scheme 2 Plausible mechanism for the triethylamine-induced cy-
cloisomerization reaction
1H NMR (400 MHz, CDCl3): d = 3.73 (s, 2 H, SCH2), 6.80 (d,
J = 1.6 Hz, 1 H, ArH), 7.12 (t, J = 8.0 Hz, 1 H, ArH), 7.22 (t, J = 7.2
Hz, 1 H, ArH), 7.26–7.28 (m, 3 H, ArH), 7.33 (d, J = 8.0 Hz, 2 H,
ArH), 7.60 (d, J = 8.0 Hz, 1 H, ArH), 8.32 (br s, 1 H, NH).
In conclusion, we have developed an efficient and ex-
tremely useful method for the regioselective synthesis of
3-benzylthiazolo[3,2-a]indole from 2-(prop-2-ynylthio)-
1H-indole via in situ sequential Sonogashira acetylide-
coupling followed by triethylamine-induced heteroannu-
lation reaction. The cycloisomerization reaction does not
require any transition metal catalyst. The method is sim-
ple and straightforward and provides an easy access to the
thiazoloindole derivatives.
MS: m/z for C17H12ClNS = 298 [M+ + H].
3n
Yield: 158 mg (75%); viscous liquid.
IR (neat): 2220, 3353 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.72 (s, 2 H, SCH2), 6.80 (s, 1 H,
ArH), 7.12 (t, J = 7.2 Hz, 1 H, ArH), 7.20–7.24 (m, 1 H, ArH), 7.26
(br s, 5 H, ArH), 7.32 (d, J = 8.4 Hz, 1 H, ArH), 7.59 (d, J = 8.0 Hz,
1 H, ArH), 8.31 (br , 1 H, NH).
Melting points were determined in open capillaries and are uncor-
rected. IR spectra were recorded on a PerkinElmer L 120-000A
spectrometer (cm–1) on KBr disks. 1H NMR and 13C NMR spectra
were recorded on a Bruker DPX-400 and Bruker DPX-300 spec-
trometers in CDCl3 with TMS as internal standard. Silica gel (60–
120 mesh and 230–400 mesh, Spectrochem, India) were used for
chromatographic separation. Silica gel G and silica gel GF-254
(Spectrochem, India) were used for TLC. Petroleum ether (PE) re-
fers to the fraction boiling between 60–80 °C. Indole-2-yl prop-2-
ynyl sulfide (1a) was prepared according to the published proce-
dure.10c
MS: m/z for C17H13NS = 264 [M+ + H].
3-(4-Acetylbenzyl)thiazolo[3,2-a]indole(4a);TypicalProcedure
1
Compound 3a (100 mg, 0.32 mmol) was dissolved in DMF (5 mL)
and Et3N (2 mL, 14.3 mmol) was added. The reaction mixture was
heated at 90 °C for 4 h. After completion of the reaction, H2O (5
mL) was added and the mixture was extracted with CH2Cl2 (3 × 15
mL). The combined organic extracts were washed with H2O (3 × 15
mL) followed by brine (15 mL), and dried (Na2SO4). Evaporation
of the solvent furnished a crude mass, which was purified by col-
umn chromatography over silica gel. Elution of the column with
EtOAc–PE (5:95) afforded the product 4a.
Sonogashira Coupling Reaction; 1-{4-[3-(1H-indol-2-ylsul-
fanyl)prop-1-ynyl]phenyl}ethan-1-one (3a); Typical Procedure
A mixture of 4-iodoacetophenone (2a; 197 mg, 0.80 mmol),
Pd(PPh3)2Cl2 (10.08 mg, 0.0144 mmol), CuI (2.7 mg, 0.0144
mmol), and Et3N (1.0 mL, 12.2 mmol) in anhyd DMF (5 mL) was
stirred at r.t. under N2 atmosphere. Indol-2-yl prop-2-ynyl sulfide
(1a; 150 mg, 0.80 mmol) was then added and the mixture was
stirred at r.t. for 3 h. After completion of the reaction as monitored
by TLC, H2O (10 mL) was added. The mixture was extracted with
CH2Cl2 (3 × 15 mL) and the combined organic layers were washed
successively with H2O (3 × 15 mL) and brine (20 mL), and dried
(Na2SO4). Evaporation of the solvent furnished a crude mass, which
was purified by column chromatography over silica gel. Elution of
One-Pot Preparation of 3-(4-Acetylbenzyl)thiazolo[3,2-a]indole
(4a); Typical Procedure 2
A mixture of 4-iodoacetophenone (2a; 197 mg, 0.80 mmol),
Pd(PPh3)2Cl2 (10.08 mg, 0.0144 mmol), CuI (2.7 mg, 0.0144
mmol), and Et3N (1.0 mL, 12.2 mmol) in anhyd DMF (5 mL) was
stirred at r.t. under N2 atmosphere. Indol-2-yl prop-2-ynyl sulfide
(1a; 150 mg, 0.80 mmol) was then added to the mixture and the
mixture was stirred at r.t. for 3 h. After completion of the reaction
as monitored by TLC, the reaction mixture was heated at 90 °C for
4 h. H2O (10 mL) was added to the mixture and extracted with
CH2Cl2 (3 × 15 mL). The combined organic layers were washed
successively with H2O (3 × 15 mL) and brine (20 mL), and dried
Synthesis 2011, No. 9, 1413–1418 © Thieme Stuttgart · New York

PAPER
Synthesis of 3-Benzylthiazolo[3,2-a]indoles
1417
(Na2SO4). Evaporation of CH2Cl2 furnished a crude mass, which
was purified by column chromatography over silica gel. Elution of
the column with EtOAc–PE (5:95) afforded the product 4a as a col-
orless solid; yield: 82 mg (82%); mp 110 °C.
1H NMR (400 MHz, CDCl3): d = 2.52 (s, 3 H, ArCH3), 4.54 (s, 2 H,
ArCH2), 6.04 (s, 1 H, =CH), 6.59 (s, 1 H, ArH), 6.97 (quint, J = 6.8
Hz, 2 H, ArH), 7.38 (d, J = 8.0 Hz, 1 H, ArH), 7.47 (d, J = 8.4 Hz,
2 H, ArH), 8.21 (d, J = 8.4 Hz, 2 H, ArH).
IR (KBr): 1672 cm–1.
13C NMR (400 MHz, CDCl3): d = 19.0, 34.7, 90.3, 106.8, 108.6,
119.4, 121.3, 124.2, 129.2, 129.4, 129.6, 132.6, 133.1, 138.1, 143.7,
147.3.
1H NMR (400 MHz, CDCl3): d = 2.62 (s, 3 H, COCH3), 4.49 (s, 2
H, ArCH2), 5.97 (s, 1 H, =CH), 6.57 (s, 1 H, ArH), 7.03 (t, J = 8.0
Hz, 1 H, ArH), 7.18 (t, J = 7.6 Hz, 1 H, ArH), 7.41 (d, J = 8.0 Hz, 2
H, ArH), 7.61 (dd, J = 8.0, 2.8 Hz, 2 H, ArH), 7.95 (d, J = 8.0 Hz, 2
H, ArH).
HRMS: m/z calcd for C18H14N2O2S: 345.0674 [M + Na]+; found:
345.0676 [M + Na]+.
4f
13C NMR (400 MHz, CDCl3): d = 26.6, 34.9, 91.6, 106.3, 111.2,
119.1, 119.8, 121.1, 129.0, 129.1, 129.9, 133.2, 133.5, 136.2, 138.8,
141.5, 197.6.
Yield: 197 mg (80%); greenish yellow solid; mp 170 °C.
IR (KBr): 1528 cm–1.
HRMS: m/z calcd for C19H15NOS + Na: 328.0772 [M + Na]+;
1H NMR (400 MHz, CDCl3): d = 4.55 (s, 2 H, ArCH2), 5.98 (s, 1
H, =CH), 6.58 (s, 1 H, ArH), 7.05 (t, J = 7.6 Hz, 1 H, ArH), 7.19 (t,
J = 7.6 Hz, 1 H, ArH), 7.54 (t, J = 8.0 Hz, 1 H, ArH), 7.62 (t, J = 8.0
Hz, 3 H, ArH), 8.18 (d, J = 8.0 Hz, 1 H, ArH), 8.23 (s, 1 H, ArH).
found: 328.0775 [M + Na]+.
4b
Yield: 200 mg (78%); colorless solid; mp 145 °C.
IR (KBr): 1678 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.56 (s, 3 H, ArCH3), 2.58 (s, 3 H,
COCH3), 4.48 (s, 2 H, ArCH2), 5.97 (s, 1 H, =CH), 6.57 (s, 1 H,
ArH), 6.95–7.00 (m, 2 H, ArH), 7.40 (d, J = 8.0 Hz, 2 H, ArH), 7.46
(d, J = 8.0 Hz, 1 H, ArH), 7.94 (d, J = 7.6 Hz, 2 H, ArH).
13C NMR (400 MHz, CDCl3): d = 34.6, 91.8, 106.8, 111.0, 119.2,
119.9, 121.2, 122.6, 123.9, 129.8, 130.0, 133.0, 133.2, 134.9, 138.1,
138.8, 148.7.
MS: m/z for C17H12N2O2S = 309 [M+ + H].
4g
Yield: 154 mg (60%); viscous gum.
IR (KBr): 1525 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.56 (s, 3 H, ArCH3), 4.54 (s, 2 H,
ArCH2), 5.99 (s, 1 H, =CH), 6.58 (s, 1 H, ArH), 7.01 (d, J = 6.4 Hz,
1 H, ArH), 7.45 (d, J = 8.0 Hz, 1 H, ArH), 7.52–7.54 (m, 1 H, ArH),
7.63 (d, J = 8.2 Hz, 2 H, ArH), 8.17 (d, J = 8.0 Hz, 1 H, ArH), 8.23
(s, 1 H, ArH).
13C NMR (400 MHz, CDCl3): d = 19.0, 26.7, 34.9, 90.1, 106.3,
108.8, 119.2, 121.2, 129.1, 129.5, 133.1, 133.6, 136.2, 138.3, 141.6,
197.7.
HRMS: m/z calcd for C20H17NOS + Na: 342.0929 [M + Na]+;
found: 342.0921 [M + Na]+.
4c
Yield: 88 mg (82%); colorless solid; mp 95 °C.
4h
IR (KBr): 1712 cm–1.
Yield: 175 mg (65%); viscous gum.
IR (KBr): 1528 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.39 (s, 3 H, ArCH3), 2.56 (s, 3 H,
ArCH3), 4.54 (s, 2 H, ArCH2), 5.99 (s, 1 H, =CH), 6.58 (s, 1 H,
ArH), 7.01 (d, J = 6.8 Hz, 1 H, ArH), 7.45 (d, J = 8.0 Hz, 1 H, ArH),
7.65 (d, J = 8.4 Hz, 2 H, ArH), 8.19–8.21 (m, 1 H, ArH), 8.23 (s, 1
H, ArH).
1H NMR (400 MHz, CDCl3): d = 1.38 (t, J = 7.2 Hz, 3 H, CH2CH3),
4.37 (q, J = 7.2 Hz, 2 H, CH2CH3), 4.48 (s, 2 H, ArCH2), 5.94 (s, 1
H, =CH), 6.56 (s, 1 H, ArH), 7.03 (t, J = 7.6 Hz, 1 H, ArH), 7.18 (t,
J = 7.2 Hz, 1 H, ArH), 7.38 (d, J = 8.0 Hz, 2 H, ArH), 7.62 (d,
J = 8.4 Hz, 2 H, ArH), 8.04 (d, J = 8.4 Hz, 2 H, ArH).
13C NMR (400 MHz, CDCl3): d = 14.4, 35.0, 61.1, 91.5, 106.2,
111.2, 119.1, 119.7, 121.1, 128.9, 129.6, 129.9, 130.2, 133.2, 133.7,
138.8, 141.1, 166.3.
4i
HRMS: m/z calcd for C20H17NO2S + Na: 358.0878 [M + Na]+;
Yield: 200 mg (70%); viscous gum.
IR (KBr): 1525 cm–1.
found: 358.0876 [M + Na]+.
4d
1H NMR (400 MHz CDCl3): d = 2.78 (s, 3 H, ArCH3), 4.52 (s, 2 H,
ArCH2), 5.76 (s, 1 H, =CH), 6.59 (s, 1 H, ArH), 6.86 (d, J = 7.6 Hz,
1 H, ArH), 7.47 (s, 1 H, ArH), 7.56 (d, J = 6.0 Hz, 2 H, ArH), 8.19–
8.21 (m, 2 H, ArH).
Yield: 210 mg (85%); yellow solid; mp 155 °C.
IR (KBr): 1519 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.54 (s, 2 H, ArCH2), 6.02 (s, 1
H, =CH), 6.58 (s, 1 H, ArH), 7.03 (t, J = 7.6 Hz, 1 H, ArH), 7.19 (t,
J = 7.6 Hz, 1 H, ArH), 7.48 (d, J = 8.4 Hz, 2 H, ArH), 7.54 (d,
J = 8.4 Hz, 1 H, ArH), 7.63 (d, J = 8.0 Hz, 1 H, ArH), 8.21 (d,
J = 8.4 Hz, 2 H, ArH).
4j
Yield: 245 mg (80%); viscous gum.
IR (KBr): 1716 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.40 (t, J = 7.0 Hz, 3 H, CH2CH3),
2.77 (s, 3 H, ArCH3), 4.39 (q, J = 7.1 Hz, 2 H, CH2CH3), 4.47 (s, 2
H, ArCH2), 5.78 (s, 1 H, =CH), 6.57 (s, 1 H, ArH), 6.88 (d, J = 1.6
Hz, 1 H, ArH), 7.29–7.31 (m, 2 H, ArH), 7.45 (d, J = 2.4 Hz, 1 H,
ArH), 8.02–8.05 (m, 2 H, ArH).
13C NMR (400 MHz, CDCl3): d = 34.7, 91.8, 106.8, 110.9, 119.2,
119.9, 121.3, 124.2, 129.6, 129.7, 132.6, 133.2, 138.7, 143.6, 147.3.
HRMS: m/z calcd for C17H12N2O2S: 331.0517 [M + Na]+; found:
331.0523 [M + Na]+.
4e
4k
Yield: 193 mg (75%); yellow solid; mp 135 °C.
IR (KBr): 1519 cm–1.
Yield: 206 mg (75%); viscous gum.
IR (KBr): 1520 cm–1.
Synthesis 2011, No. 9, 1413–1418 © Thieme Stuttgart · New York

1418
K. C. Majumdar, S. Nath
PAPER
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1H NMR (400 MHz, CDCl3): d = 4.60 (s, 2 H, ArCH2), 6.09 (s, 1
H, =CH), 6.60 (s, 1 H, ArH), 7.03 (t, J = 8.0 Hz, 1 H, ArH), 7.19 (t,
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J = 8.0 Hz, 1 H, ArH), 7.63 (d, J = 2.4 Hz, 1 H, ArH), 8.02 (dd,
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4l
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Yield: 208 mg (73%); viscous gum.
IR (KBr): 1520 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.52 (s, 3 H, ArCH3), 4.59 (s, 2 H,
ArCH2), 6.10 (s, 1 H, =CH), 6.60 (s, 1 H, ArH), 6.95 (t, J = 8.0 Hz,
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Acknowledgment
We thank the CSIR (New Delhi) and DST (New Delhi) for financial
assistance.
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Synthesis 2011, No. 9, 1413–1418 © Thieme Stuttgart · New York