Copper(II) triflate promoted one-pot synthesis of coumarin-, quinolone-, and naphthalene-annulated 2-aminothiazoles under ligand-free conditions

Article abstract of DOI:10.1055/s-0031-1289608

An efficient synthesis of new 2-aminothiazole-annulated compounds is described via copper(II) triflate promoted sequential condensation, arylation, and heterocyclization reactions in one step. The reaction is compatible with a variety of substrates provid

Full text of DOI:10.1055/s-0031-1289608

PAPER
87
Copper(II) Triflate Promoted One-Pot Synthesis of Coumarin-, Quinolone-,
and Naphthalene-Annulated 2-Aminothiazoles under Ligand-Free Conditions
O
ne-Pot Synthesis
.
of
A
nnulate
C
d 2-Aminothiazo
.
les Majumdar,*a,b Nirupam De,a Debankan Ghosh,a Sudipta Ponra,a B. Roya
a
Department of Chemistry, University of Kalyani, Kalyani 741235, W.B., India
Department of Chemical Sciences, Tezpur University, Napaam 784028, Assam, India
E-mail: kcm_ku@yahoo.co.in
b
Received 12 September 2011; revised 22 October 2011
catalyzed methods have been developed for their synthe-
sis, but most require either expensive catalytic systems or
a variety of ligands or complex precursors not easy to syn-
thesize.11,12 In some reports the amino group was intro-
Abstract: An efficient synthesis of new 2-aminothiazole-annulated
compounds is described via copper(II) triflate promoted sequential
condensation, arylation, and heterocyclization reactions in one step.
The reaction is compatible with a variety of substrates providing ef-
ficient access to many biologically important skeletons in good duced at the 2-position of the benzothiazole moiety in a
separate step.13 Thus, the synthesis of coumarin-, quino-
yields.
lone-, and naphthalene-annulated 2-aminothiazoles by a
simple, step-economic, less hazardous methodology is
still outstanding. In recent years, there has been increased
attention in the design and implementation of multicom-
ponent reactions (MCR) for the construction of diverse
heterocyclic scaffolds, as these fulfill present-day require-
ments, such as the use of simple and readily available
starting materials and step- and atom-economic synthesis
involving minimal human resource, energy etc.14 In this
context, in continuation our interest in the synthesis of
bioactive heterocyclic scaffolds,15 we undertook a study
to synthesize important scaffolds, carbo- and heterocycle-
annulated 2-aminothiazoles, via a copper(II) triflate pro-
moted MCR approach. Herein we report our results.
Key words: copper triflate, multicomponent reaction, naphthothia-
zole, domino synthesis, carbon disulfide
Heterocyclic compounds are important structural units
useful in medicinal chemistry and valuable as synthetic
organic building blocks. Among the various heterocycles,
the 2-aminothiazole subunit has great pharmaceutical im-
portance due to its presence (annulated with other carbo-
and heterocycles) in a broad range of natural and synthetic
compounds of biological interest.1–3 For example, cou-
marin- and quinolone-annulated 2-aminothiazole com-
pounds can act as effective anti-inflammatory and
analgesic agents,4 naphthothiazole-based mono-methine
cyanine dye is used as an effective staining tool for the vi-
sualization of macromolecules such as DNA,5 and naph-
thothiazole-containing carboxamides can act as novel
antitumor agents and DNA photocleavers.6 Both com-
pounds I and II (Figure 1) showed potent anticonvulsant
activity.7,8
Most recently, Ma et al. described the copper(II) chloride
catalyzed domino synthesis of 2-aminobenzothiazoles.16
To explore the scope of this methodology in achieving our
target compounds we started with the reaction of 6-amino-
5-bromocoumarin (1a) with carbon disulfide and pyrroli-
dine using copper(II) chloride dihydrate. Unfortunately,
the desired coupling product, coumarin-annulated 2-ami-
nothiazoles 4a, was obtained in poor yield (only 21%).
We envisioned that a ligand might be necessary to im-
prove the yield of the reaction. We then tried the reaction
using L-proline or 1,10-phenanthroline as ligands in sepa-
rate experiments, but no improvement of the yield was ob-
served. We, therefore, modified the reaction conditions by
changing the copper salts through a series of experiments
(Table 1). After several attempts, the reaction afforded the
desired product 4a in 81% yield using copper(II) triflate
(1.0 equiv) and potassium carbonate (3.0 equiv) at 120 °C
in N,N-dimethylformamide (entry 6). It was also found
that the concentration of copper(II) triflate may be re-
duced to 0.5 equivalents without affecting yield of the
product. Other copper sources such as copper(I) chloride,
bromide, or iodide were found to be less effective (entries
2–4). The reaction failed completely when copper(II)
acetate was used (entry 5). Further screening of bases did
not improve the efficiency of this reaction (entries 11 and
12). The coupling product was also formed without using
any base, but in trace amounts. Among several solvents
R2
R1
S
N
N
NH
O
N
N
NH
S
S
HO
N
O
O
I
II
Figure 1 2-Aminochromenothiazole and 2-aminonaphthothiazole
derivatives: anticonvulsant agents
In most methods reported so far for the synthesis of 2-ami-
nothiazole-annulated compounds, phenylureas have been
frequently used as key intermediates and harmful bromine
has been used for cyclization.9,10 Recently, some metal-
SYNTHESIS 2012, 44, 87–92
x
x.
x
x
.
2
0
1
1
Advanced online publication: 15.11.2011
DOI: 10.1055/s-0031-1289608; Art ID: Z88811SS
© Georg Thieme Verlag Stuttgart · New York

88
K. C. Majumdar et al.
PAPER
Table 2 7H-Chromeno[6,5-d][1,3]thiazoles and [1,3]Thiazolo[5,4-
f]quinolines by Annulation of 6-Amino-5-bromo-substituted Quino-
lones and Coumarinsa
N,N-dimethylformamide was found to be superior to di-
methylacetamide and dimethyl sulfoxide while acetoni-
trile and toluene were found to be ineffective (entry 6 vs.
entries 7–10).
R2
Br
H2N
N
S
(i)
R1
Table 1 Optimization of the Reaction Conditionsa
O
N
X
X
O
Entry
1
Promoterb
CuCl2·2H2O
CuCl
Solvent
DMF
Base
Yieldc (%)
1a X = O 1b X = NMe
1c X = NEt
4a–j
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Na2CO3
21d
15
18
trace
0
Entry Product
Yield (%)
81
2
DMF
N
S
3
CuBr
DMF
1
2
4a
4b
O
N
O
4
CuI
DMF
5
Cu(OAc)2
DMF
e
N
S
6
Cu(OTf)2
DMF
81
0
74
65
O
7
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
MeCNf
DMA
toluene
DMSO
DMF
N
O
8
58
0
N
S
9
3
4c
O
N
O
10
11
12
35
72
40
Et
N
S
4
5
4d
4e
83
75
DMF
O
N
a Reaction conditions: 1a (1.0 mmol), pyrrolidine (1.5 mmol), CS2
(1.2 mmol), base (3.0 mmol), Cu salt (1.0 mmol), anhyd solvent (5
mL), 120 °C, 8 h.
O
Et
N
b Unless otherwise stated promoter (1.0 equiv) was used.
c Isolated yield.
S
O
d Results using entry 1 with various ligands are not shown.
e Promoter (0.5 equiv) was used.
O
N
MeO
f Reflux temperature.
N
S
6
4f
69
78
O
With the optimized conditions in hand, the scope of this
methodology was extended to different amine sources and
other heterocyclic systems. The results show that the pre-
cursors 1a–c successfully gave the desired 2-aminothiaz-
ole derivatives 4a–j in good yields (Table 2). It was also
found that 3-amino-4-iodocoumarin (1d) reacted smooth-
ly to afford the cyclized products 4k–l in high yields
(Table 3).
N
N
Me
N
S
7
8
4g
O
N
N
Me
Et
N
Encouraged by these results, we next chose naphthalene
systems as precursors. Both 1-amino-2-bromonaphtha-
lene (1e) and 2-amino-1-bromonaphthalene (1f) afforded
the 2-aminothiazole derivatives 4m–o in moderate yields.
Thus, the same protocol also worked well for naphthalene
systems in addition to heterocyclic systems (Table 4).
S
4h
4i
81
86
O
N
N
Me
O
N
S
9
The formation of the products 4 has been rationalized by
the initial formation of dithiocarbamic acids17 by the reac-
tion of carbon disulfide with the amine. Such acids are
very unstable, so they instantly react with potassium car-
bonate forming dithiocarbamate salts18 which in turn
undergo Ullmann-type coupling reaction with the o-halo-
amine-annulated compounds in the presence of copper(II)
triflate promoter to afford the dithiocarbamate 2. It is
noteworthy that the reaction occurs in the absence of a
ligand although a ligand is usually required for such type
N
N
N
Et
N
S
O
10
4j
81
N
Et
a Reaction conditions: (i) 1a–c (1.0 mmol), CS2 (1.2 mmol), amine
(1.5 mmol), K2CO3 (3.0 mmol), Cu(OTf)2 (0.5 mmol), anhyd DMF (5
mL), 120 °C, 6–9 h.
Synthesis 2012, 44, 87–92
© Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Annulated 2-Aminothiazoles
89
Table 3 4H-Chromeno[3,4-d][1,3]thiazoles by Annulation of a 3-
Br
R2
Amino-4-iodo-substituted Coumarina
S
H2N
N
R1
R1
R2
R1
S
I
N
H
••
N
S
S
SK
R2
R2
H2N
NH2
O
1
K2CO3
(i)
+
N
N
Cu(OTf)2
R1
CS2
O
O
2
1d
4k,l
O
Entry
1
Product
Yield (%)
R2
R2
N
R1
H2S
SH
N
R1
S
S
N
S
HN
N
4k
80
83
N
O
O
4
3
Et
N
Scheme 1 Probable mechanistic route
S
2
4l
N
In summary, we have developed a convenient and effi-
cient protocol that provides an easy access to a variety of
coumarin-, quinolone- and naphthalene-annulated 2-ami-
nothiazoles in good yields from simple starting materials.
Closely related analogues of the synthesized compounds4–8
possess potential bioactivity. The methodology is step
economic and less hazardous. The synthesized com-
pounds with the synthetic strategy as well would be useful
to the pharmacologists and medicinal chemists.
O
O
a Reaction conditions: (i) 1d (1.0 mmol), CS2 (1.2 mmol), amine (1.5
mmol), K2CO3 (3.0 mmol), Cu(OTf)2 (0.5 mmol), anhyd DMF (5
mL), 120 °C, 6 h.
Table 4 Naphtho[1,2-d][1,3]thiazoles and Naphtho[2,1-d][1,3]thia-
zoles by Annulation of 1-Amino-2-bromo- and 2-Amino-1-bro-
monaphthalenesa
R2
All chemicals were procured from either Sigma Aldrich Chemicals
Pvt. Ltd. or Spectrochem, India. Melting points were determined in
open capillaries and are uncorrected. IR spectra were recorded on a
Perkin-Elmer L 120-000A spectrophotometer on KBr disks. 1H and
13C NMR spectra were recorded on a Bruker DPX-400 spectrometer
in CDCl3 with TMS as internal standard. CHN was recorded on a
Perkin-Elmer 2400 series II CHN analyzer. MS(ESI) were recorded
on a Q-TOF micro instrument. HRMS(ESI) were recorded on a
QTOF MicroYA 263. Silica gel [(60–120, 230–400 mesh),
Rankem, India] was used for chromatographic separation. Silica gel
(GF-254) was used for TLC. Petroleum ether (PE) has bp 60–80 °C.
NH2
Br
N
S
R1
Br
or
NH2
(i)
N
1e
1f
4m–o
Entry
Product
Yield (%)
49
N
N
1
2
3
4m
S
2-Pyrrolidin-1-yl-7H-chromeno[6,5-d][1,3]thiazol-7-one (4a);
Typical Procedure
A mixture of CS2 (1.2 mmol), pyrrolidine (1.5 mmol), and K2CO3
(3 mmol) was stirred in DMF (5 mL) at r.t. for 10 min. Then 6-ami-
no-5-bromocoumarin 1a (1 mmol) and Cu(OTf)2 (0.5 mmol) were
added to the solution. The mixture was then heated with stirring at
120 °C for 8 h. The solution was allowed to cool to r.t., and parti-
tioned between EtOAc and H2O. The organic layer was collected,
washed with H2O and brine, and dried (Na2SO4). The solvent was
removed under reduced pressure to give a crude mass, which was
purified by column chromatography (silica gel) to afford 4a as a
green solid; yield: 220 mg (81%); mp 256–258 °C.
N
S
4n
4o
77
80
N
Et
N
S
N
IR (KBr): 1550, 1622, 1712, 2872 cm–1.
a Reaction conditions: (i) 1e/1f (1.0 mmol), CS2 (1.2 mmol), amine
(1.5 mmol), K2CO3 (3.0 mmol), Cu(OTf)2 (0.5 mmol), anhyd DMF (5
mL), 120 °C, 6–7 h.
1H NMR (400 MHz, CDCl3): d = 2.12 (br s, 4 H), 3.60 (br s, 4 H),
6.49 (d, J = 9.6 Hz, 1 H), 7.29 (d, J = 9.2 Hz, 1 H), 7.69 (d, J = 9.2
Hz, 1 H), 7.71 (d, J = 9.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 25.7, 49.8, 112.7, 115.1, 116.7,
of coupling. The cyclization may occurs by the nucleo-
philic attack of the amino group of 2 to the C=S bond to
form the cyclic intermediates 3, which on subsequent
elimination of hydrogen sulfide may finally give the de-
sired cyclic products 4 (Scheme 1).
121.8, 128.0, 141.0, 149.1, 150.3, 160.8, 164.7.
MS (ESI): m/z = 273.00 [M + H]+.
Anal. Calcd for C14H12N2O2S: C, 61.75; H, 4.44; N, 10.29. Found:
C, 61.58; H, 4.51; N, 10.41.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 87–92

90
K. C. Majumdar et al.
PAPER
Compound 4b
13C NMR (100 MHz, CDCl3): d = 20.3, 29.9, 51.1, 112.3, 114.3,
121.3, 121.8, 128.2, 134.6, 136.1, 148.7, 161.8, 164.7.
Greenish yellow solid; yield: 212 mg (74%); mp 140–142 °C.
IR (KBr): 1540, 1618, 1722, 2860 cm–1.
MS (ESI): m/z = 316.07 [M + H]+, 338.05 [M + Na]+.
1H NMR (400 MHz, CDCl3): d = 1.72 (br s, 6 H), 3.62 (br s, 4 H),
6.47 (d, J = 9.6 Hz, 1 H), 7.25 (d, J = 8.8 Hz, 1 H), 7.63 (d, J = 8.8
Hz, 1 H), 7.69 (d, J = 9.6 Hz, 1 H).
Anal. Calcd for C17H21N3OS: C, 64.73; H, 6.71; N, 13.32. Found:
C, 64.91; H, 6.62; N, 13.27.
Compound 4g
13C NMR (100 MHz, CDCl3): d = 24.1, 25.3, 49.8, 112.6, 114.9,
Greenish yellow solid; yield: 233 mg (78%); mp 166–168 °C.
IR (KBr): 1538, 1612, 1645, 2855 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.72 (br s, 6 H), 3.63 (br s, 4 H),
3.76 (s, 3 H), 6.78 (d, J = 9.6 Hz, 1 H), 7.32 (d, J = 8.8 Hz, 1 H),
7.67 (d, J = 9.6 Hz, 1 H), 7.73 (d, J = 8.8 Hz, 1 H).
116.6, 121.9, 127.9, 140.9, 149.2, 149.9, 160.8, 168.3.
MS (ESI): m/z = 287.06 [M + H]+, 309.04 [M + Na]+.
Anal. Calcd for C15H14N2O2S: C, 62.92; H, 4.93; N, 9.78. Found: C,
63.03; H, 4.99; N, 9.62.
Compound 4c
Brown solid; yield: 196 mg (65%); mp 144–146 °C.
13C NMR (100 MHz, CDCl3): d = 24.2, 25.3, 29.9, 49.8, 112.8,
114.5, 121.3, 122.0, 129.8, 135.2, 136.0, 148.2, 161.6, 164.5.
IR (KBr): 1545, 1619, 1730, 2873 cm–1.
MS (ESI): m/z = 300.04 [M + H]+, 322.03 [M + Na]+.
1H NMR (400 MHz, CDCl3): d = 1.45 (s, 12 H), 3.96–3.99 (m, 2 H),
6.45 (d, J = 9.6 Hz, 1 H), 7.23 (d, J = 8.8 Hz, 1 H), 7.62 (d, J = 8.8
Hz, 1 H), 7.71 (d, J = 9.6 Hz, 1 H).
Anal. Calcd for C16H17N3OS: C, 64.19; H, 5.72; N, 14.04. Found:
C, 64.33; H, 5.73; N, 13.95.
Compound 4h
Yellow solid; yield: 271 mg (81%); mp 142–144 °C.
IR (KBr): 1542, 1614, 1654, 2865 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.33 (t, J = 7.2 Hz, 3 H), 3.75 (s,
3 H), 4.12 (q, J = 7.2 Hz, 2 H), 6.69 (d, J = 9.2 Hz, 1 H), 7.31 (d,
J = 8.8 Hz, 1 H), 7.40–7.45 (m, 3 H), 7.49–7.54(m, 3 H), 7.77 (d,
J = 9.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 13.2, 29.9, 47.8, 112.7, 114.3,
121.6, 121.9, 127.9, 128.3, 129.5, 130.3, 135.5, 135.8, 143.9, 148.2,
161.8, 167.5.
13C NMR (100 MHz, CDCl3): d = 20.3, 51.4, 112.4, 114.6, 116.4,
121.8, 127.2, 141.3, 148.9, 150.3, 160.9, 164.9.
MS (ESI): m/z = 303.05 [M + H]+, 325.02 [M + Na]+.
Anal. Calcd for C16H18N2O2S: C, 63.55; H, 6.00; N, 9.26. Found: C,
63.74; H, 5.89; N, 9.17.
Compound 4d
Greenish yellow solid; yield: 267 mg (83%); mp 198–200 °C.
IR (KBr): 1534, 1619, 1723, 2870 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.32 (t, J = 7.2 Hz, 3 H), 4.12 (q,
J = 7.2 Hz, 2 H), 6.40 (d, J = 9.6 Hz, 1 H), 7.27 (d, J = 8.8 Hz, 1 H),
7.40 (d, J = 7.6 Hz, 2 H), 7.45 (m, 1 H), 7.52 (d, J = 7.6 Hz, 2 H),
7.56 (d, J = 9.6 Hz, 1 H), 7.71 (d, J = 8.8 Hz, 1 H).
MS (ESI): m/z = 336.00 [M + H]+, 357.97 [M + Na]+.
Anal. Calcd for C19H17N3OS: C, 68.03; H, 5.11; N, 12.53. Found:
C, 68.22; H, 5.02; N, 12.49.
13C NMR (100 MHz, CDCl3): d = 13.1, 47.9, 112.4, 114.9, 116.6,
122.1, 127.9, 128.4, 128.5, 130.3, 140.9, 143.7, 149.5, 149.8, 160.7,
167.7.
Compound 4i
Yellow solid; yield: 269 mg (86%); mp 176–178 °C.
IR (KBr): 1535, 1614, 1651, 2855 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.38 (t, J = 7.2 Hz, 3 H), 1.72 (br
s, 6 H), 3.63 (br s, 4 H), 4.41 (q, J = 7.2 Hz, 2 H), 6.76 (d, J = 9.6
Hz, 1 H), 7.34 (d, J = 9.2 Hz, 1 H), 7.65 (d, J = 9.6 Hz, 1 H), 7.71
(d, J = 9.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 12.9, 24.2, 25.3, 37.7, 49.8, 112.6,
114.7, 121.4, 122.1, 129.1, 134.1, 135.8, 148.1, 161.3, 165.2.
MS (ESI): m/z = 323.01 [M + H]+, 345.00 [M + Na]+.
Anal. Calcd for C18H14N2O2S: C, 67.06; H, 4.38; N, 8.69. Found: C,
67.13; H, 4.27; N, 8.76.
Compound 4e
Greenish yellow solid; yield: 264 mg (75%); mp 192–194 °C.
IR (KBr): 1533, 1607, 1714, 2856 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.29 (t, J = 7.0 Hz, 3 H), 3.88 (s,
3 H), 4.06 (q, J = 7.0 Hz, 2 H), 6.40 (d, J = 9.6 Hz, 1 H), 7.03 (d,
J = 8.8 Hz, 2 H), 7.25 (d, J = 8.8 Hz, 1 H), 7.30 (d, J = 8.8 Hz, 2 H),
7.55 (d, J = 9.6 Hz, 1 H), 7.69 (d, J = 8.8 Hz, 1 H).
MS (ESI): m/z = 314.08 [M + H]+, 336.06 [M + Na]+.
Anal. Calcd for C17H19N3OS: C, 65.15; H, 6.11; N, 13.41. Found:
C, 65.06; H, 6.15; N, 13.47.
Compound 4j
Green solid; yield: 242 mg (81%); mp 234–236 °C.
IR (KBr): 1542, 1618, 1661, 2855 cm–1.
13C NMR (100 MHz, CDCl3): d = 13.1, 47.8, 55.6, 112.4, 114.8,
115.5, 116.5, 122.0, 128.6, 129.6, 136.4, 140.9, 149.4, 150.0, 159.6,
160.7, 168.6.
MS (ESI): m/z = 352.97 [M + H]+, 374.95 [M + Na]+.
1H NMR (400 MHz, CDCl3): d = 1.39 (t, J = 7.2 Hz, 3 H), 2.10–
2.13 (m, 4 H), 3.61 (t, J = 6.4 Hz, 4 H), 4.41 (q, J = 7.2 Hz, 2 H),
6.76 (d, J = 9.6 Hz, 1 H), 7.35 (d, J = 9.2 Hz, 1 H), 7.67 (d, J = 9.6
Hz, 1 H), 7.77 (d, J = 9.2 Hz, 1 H).
Anal. Calcd for C19H16N2O3S: C, 64.76; H, 4.58; N, 7.95. Found: C,
64.59; H, 4.61; N, 8.07.
Compound 4f
Yellow solid; yield: 217 mg (69%); mp 154–156 °C.
13C NMR (100 MHz, CDCl3): d = 12.9, 25.7, 37.7, 49.7, 112.7,
114.8, 121.3, 122.0, 129.0, 133.9, 135.9, 148.5, 161.3, 164.5.
IR (KBr): 1545, 1612, 1662, 2883 cm–1.
HRMS (TOF, ES+): m/z [M + Na]+ calcd for C16H17N3NaOS:
322.0990; found: 322.0995.
1H NMR (400 MHz, CDCl3): d = 1.46 (s, 12 H), 3.76 (s, 3 H), 3.98–
4.02 (m, 2 H), 6.76 (d, J = 9.6 Hz, 1 H), 7.29 (d, J = 9.2 Hz, 1 H),
7.68 (d, J = 9.6 Hz, 1 H), 7.70 (d, J = 9.2 Hz, 1 H).
Compound 4k
Brown solid; yield: 218 mg (80%); mp 246–248 °C.
Synthesis 2012, 44, 87–92
© Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Annulated 2-Aminothiazoles
91
IR (KBr): 1559, 1602, 1723, 2852 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.12 (br s, 4 H), 3.61 (br s, 4 H),
7.27–7.37 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 25.8, 50.2, 116.8, 117.0, 123.5,
124.6, 128.5, 135.0, 137.9, 150.2, 156.0, 165.5.
MS (ESI): m/z = 272.98 [M + H]+, 294.94 [M + Na]+.
Acknowledgment
We thank CSIR (New Delhi) for financial assistance. N.D. is thank-
ful to UGC (New Delhi) and D.G. and S.P. are grateful to CSIR
(New Delhi) for fellowships. We also thank DST (New Delhi) for
providing Bruker NMR (400 MHz), Perkin-Elmer CHN Analyser,
FTIR and UV-Vis spectrometer.
Anal. Calcd for C14H12N2O2S: C, 61.75; H, 4.44; N, 10.29. Found:
C, 61.87; H, 4.38; N, 10.23.
References
(1) (a) Vicini, P.; Geronikaki, A.; Anastasia, K.; Incerti, M.;
Zani, F. Bioorg. Med. Chem. 2006, 14, 3859. (b) Caprathe,
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Compound 4l
Brown solid; yield: 267 mg (83%); mp 180–182 °C.
IR (KBr): 1538, 1604, 1733, 2872 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.29 (t, J = 7.2 Hz, 3 H), 4.18 (q,
J = 7.2 Hz, 2 H), 7.18–7.24 (m, 2 H), 7.37–7.41 (m, 4 H), 7.46 (t,
J = 7.6 Hz, 1 H), 7.54 (t, J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 13.2, 47.9, 116.5, 117.2, 123.7,
124.6, 127.7, 128.8, 128.9, 130.7, 135.9, 137.3, 143.7, 150.6, 155.9,
169.0.
MS (ESI): m/z = 323.04 [M + H]+, 345.01 [M + Na]+.
(4) (a) Kalkhambkar, R. G.; Kulkarni, G. M.; Shivkumar, H.;
Rao, N. R. Eur. J. Med. Chem. 2007, 42, 1272.
Anal. Calcd for C18H14N2O2S: C, 67.06; H, 4.38; N, 8.69. Found: C,
66.91; H, 4.44; N, 8.62.
(b) O’Kennedy, R.; Thornes, R. D. Coumarins: Biology,
Applications and Mode of Action; Wiley: Chichester, 1997.
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R. Spectrochim. Acta, Part A 2010, 75, 1605.
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3149.
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Med. Chem. 2009, 44, 203.
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Med. Chem. 2008, 16, 5377.
Compound 4m
Off-white solid; yield: 124 mg (49%); mp 79–81 °C.
IR (KBr): 1555, 1622, 2853 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.11 (br s, 4 H), 3.70 (br s, 4 H),
7.46–7.62 (m, 3 H), 7.67 (d, J = 8.8 Hz, 1 H), 7.86 (d, J = 8.4 Hz, 1
H), 8.71 (d, J = 8.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 24.7, 48.5, 117.8, 119.7, 123.0,
124.0, 124.1, 124.5, 125.7, 126.8, 131.1, 148.1, 164.9.
(9) (a) Hugerschoff, H. Chem. Ber. 1901, 34, 3121. (b)Alaimo,
R. J. J. Heterocycl. Chem. 1971, 8, 309. (c) Jeng, L.;
Kasina, S. J. Heterocycl. Chem. 1981, 18, 759.
MS (ESI): m/z = 255.04 [M + H]+.
(10) (a) Dogruer, D. S.; Unlu, S.; Sahin, M. F.; Simageahin, E. Y.
Farmaco 1998, 53, 80. (b) Naim, S. S.; Singh, S. K.;
Sharma, S. Indian J. Chem., Sect. B: Org. Chem. Incl. Med.
Chem. 1991, 30, 494. (c) Francisco, L.; Mariano, M.;
Dolores, V.; Enric, B.; Lluís, J. Tetrahedron 2004, 60, 285.
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(b) Shen, G.; Lv, X.; Bao, W. Eur. J. Org. Chem. 2009,
5897. (c) Joyce, L. L.; Evindar, G.; Batey, R. A. Chem.
Commun. 2004, 446. (d) Sahoo, S. K.; Jamir, L.; Guin, S.;
Patel, B. K. Adv. Synth. Catal. 2010, 352, 2538. (e) Saha,
P.; Ramana, T.; Purkait, N.; Ali, M. A.; Paul, R.;
Punniyamurthy, T. J. Org. Chem. 2009, 74, 8719.
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Chem. 2010, 12, 1607. (b) Wang, J.; Peng, F.; Jiang, J.; Lu,
Z.; Wang, L.; Bai, J.; Pan, Y. Tetrahedron Lett. 2008, 49,
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Anal. Calcd for C15H14N2S: C, 70.83; H, 5.55; N, 11.01. Found: C,
70.64; H, 5.56; N, 11.13.
Compound 4n
Off-white solid; yield: 206 mg (77%); mp 90–92 °C.
IR (KBr): 1541, 1616, 2850 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.72–1.77 (m, 6 H), 3.65–3.67 (m,
4 H), 7.37 (t, J = 8.0 Hz, 1 H), 7.49 (t, J = 8.0 Hz, 1 H), 7.69–7.74
(m, 3 H), 7.87 (d, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 24.2, 25.3, 49.7, 119.6, 123.6,
123.7, 124.9, 126.5, 126.6, 128.2, 128.9, 129.3, 150.8, 169.4.
MS (ESI): m/z = 269.07 [M + H]+.
Anal. Calcd for C16H16N2S: C, 71.61; H, 6.01; N, 10.44. Found: C,
71.76; H, 6.08; N, 10.51.
Compound 4o
Gummy mass; yield: 243 mg (80%).
IR (KBr): 1529, 1612, 2852 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.34 (t, J = 7.2 Hz, 3 H), 4.16 (q,
J = 7.2 Hz, 2 H), 7.34 (t, J = 7.2 Hz, 1 H), 7.39–7.45 (m, 4 H), 7.51
(t, J = 7.6 Hz, 2 H), 7.60 (d, J = 8.4 Hz, 1 H), 7.71–7.78 (m, 2 H),
7.84 (d, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 13.2, 30.9, 47.7, 119.7, 123.7,
123.8, 125.4, 126.4, 126.5, 127.8, 128.0, 128.8, 129.5, 130.2, 144.3,
150.5, 168.5.
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MS (ESI): m/z = 305.03 [M + H]+.
© Thieme Stuttgart · New York
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