An efficient synthesis of coumarin- and quinolone-annulated thiazole derivatives via ligand-free iron (III)-catalyzed coupling followed by acid-promoted condensation

Article abstract of DOI:10.1016/j.tetlet.2013.06.017

An efficient strategy for the synthesis of coumarin- and quinolone-annulated thiazole derivatives using sodium sulfide as a sulfur source has been achieved via ligand-free iron (III)-catalyzed coupling followed by acid-promoted condensation. This synthetic protocol is one-pot, less expensive, and affords the products in good yields.

Full text of DOI:10.1016/j.tetlet.2013.06.017

Tetrahedron Letters 54 (2013) 4422–4424
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An efficient synthesis of coumarin- and quinolone-annulated
thiazole derivatives via ligand-free iron (III)-catalyzed coupling
followed by acid-promoted condensation
⇑
K. C. Majumdar , Debankan Ghosh
Department of Chemistry, University of Kalyani, Kalyani 741235, W.B., India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient strategy for the synthesis of coumarin- and quinolone-annulated thiazole derivatives using
sodium sulfide as a sulfur source has been achieved via ligand-free iron (III)-catalyzed coupling followed
by acid-promoted condensation. This synthetic protocol is one-pot, less expensive, and affords the prod-
ucts in good yields.
Received 10 April 2013
Revised 3 June 2013
Accepted 6 June 2013
Available online 13 June 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Iron-catalyzed carbon–sulfur coupling
Sodium sulfide
Coumarin
Quinolone
Fused thiazoles
One-pot reaction
Compounds containing thiazole moiety gained tremendous
importance for their significant biological applications such as,
antifungal,1 antimicrobial,2 anti-inflammatory,3 antitumor,4 anti-
convulsant,5 and antitubercular6 activities. Due to their potent
activity, synthesis of thiazole and annulated thiazole derivatives
is one of the areas of current research interest. On the other hand,
coumarin and quinolone are the core moieties of many bioactive
natural products,7 and their derivatives show widespread bioactiv-
ities including antiviral, antibacterial, antimicrobial, and antifungal
properties.8 Moreover, some coumarin- and quinolone-annulated
thiazole derivatives have shown anticonvulsant and anti-inflam-
matory properties.9 There are many methodologies reported for
the synthesis of benzothiazole derivatives,10 However, coumarin-
and quinolone-annulated thiazoles are less investigated.9b,11 Re-
cently, we have reported the synthesis of coumarin-, quinolone-
annulated 2-aminothiazole derivatives by copper(II) triflate pro-
moted multicomponent reaction12 (Fig. 1).
lone-annulated heterocyclic compounds. Herein, we report our
results.
The required precursors 1a–n were prepared according to our
previously reported procedure.14h We used 1a as a model substrate
for optimizing the reaction condition for the synthesis of the de-
sired chromenothiazole derivative (2a). At first 1a was subjected
to react with Na2S (3 equiv) in DMF at 120 °C for 8–10 h using
CuI (10 mol %) as catalyst. After consumption of the starting mate-
rials as indicated by TLC, 2 ml of hydrochloric acid (12 N) was
added to the reaction mixture and was stirred for 4 h at room tem-
perature. After neutralization followed by usual work-up and chro-
matographic separation a white solid was obtained in 65% yield.
This was characterized as the desired chromenothiazole derivative
(2a) by spectral analyses. A number of experiments were per-
formed to improve the yield of the reaction by changing the cata-
lyst, solvent, and temperature of the reaction (Table 1).
After a few unsuccessful attempts the reaction was conducted
with FeCl3 (10 mol %) as catalyst in DMF at 120 °C (Table 1, entry
4), and pleasingly the yield of 2a increased to 89%. We had also ob-
served that increasing the reaction temperature or the catalyst
loading reduces the yield slightly (entries 6 and 8), while decreas-
ing the reaction temperature or catalyst loading decreases the yield
significantly (entries 5 and 7). Among the different solvents used,
DMF proved to be better over DMSO in this reaction (entry 4 vs. en-
try 3), while less polar solvents like toluene, xylene, and MeCN
were ineffective (entries 9–11). Other Lewis acid catalysts like
AlCl3 and BF3.OEt2 were also ineffective (entries 13 and 14), while
In 2009, Ma et al. reported the synthesis of benzothiazoles from
2-halobenzanilides and sodium/potassium sulfides via copper
catalysis.13 In continuation of our effort to synthesize heterocyclic
compounds by metal mediated reactions,14 we became interested
to try cheaper reagents for the synthesis of coumarin- and quino-
⇑
Corresponding author. Tel.: +91 33 25828750; fax: +91 33 25828282.
E-mail address: kcm@klyuniv.ac.in (K.C. Majumdar).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.06.017

K. C. Majumdar, D. Ghosh / Tetrahedron Letters 54 (2013) 4422–4424
4423
Previous Work :
R2
N
Cu(OTf)2 (0.5 equiv),
K2CO3,DMF, 120 oC
Br
S
R1
R2
R1
O
X
O
N
+ CS2
+
NH2
N
H
X
Present Work :
(i) FeCl3 (10 mol%),
Br
R
S
DMF, 120 o
ii) HCl, rt
C
O
X
O
+ Na2S.xH2O
R
NH
O
N
X
X= O, NMe, NEt
R, R1, R2 = alkyl or aryl group
Figure 1. Previous and present work.
Table 1
Table 2
Optimization of the reaction conditions
Synthesis of 7H-chromeno[6,5-d]thiazol-7-one and thiazolo[5,4-f]quinolin-7(6H)-one
derivatives
Ph
R
Br
H
S
N
Ph
Br
N
S
H
N
(i) conditions
(i)FeCl3 (10 mol%),
DMF, 120 oC, 8 hr.
R
N
+ Na2S.xH2O
O
(ii) HCl (12N), rt.
+ Na2S.xH2O
O
O
O
O
2a
O
(ii) HCl (12N), rt, 4h
1a
O
X
O
X
2a-n
1a-p
Entry
Catalyst (mol %)
Solvent
Temperature (°C)
Yield (%)
Entry
Substrate
X, R
Product
Yieldb (%)
1
2
CuI (10)
CuI (10)
DMF
120
120
120
120
100
140
120
120
Reflux
120
Reflux
120
120
120
120
65
41
72
89
62
83
47
85
—
—
—
20
—
—
DMSO
DMSO
DMF
DMF
DMF
DMF
DMF
Toluene
Xylene
MeCN
DMF
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
X = O, R = C6H5
X = O, R = CH3
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
—
89
81
86
82
78
82
88
86
85
74
88
83
80
77
—
3
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
FeCl3 (05)
FeCl3 (20)
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
InCl3 (10)
AlCl3 (10)
BF3ÁOEt2 (10)
—
4a
5
X = O, R = 4-MeC6H4
X = O, R = 2-MeC6H4
X = O, R = 4-OMeC6H4
X = O, R = 4-ClC6H4
X = O, R = Bn
X = NMe, R=C6H5
X = NMe, R = CH3
X = NMe, R = 4-ClC6H4
X = NEt, R = C6H5
6
7
8
9
10
11
12
13
14
15
9
10
11
12
13
14
15
16
DMF
DMF
DMF
X = NEt, R = CH3
X = NEt, R = 4-MeC6H4
X = NMe, R = 2-MeC6H4
X = O, R = 4-NO2C6H4
X = O, R = 4-OHC6H4
—
a
Optimized reaction condition.
—
—
b
Isolated yield.
InCl3 produced 2a in very low yield along with some undesired
side products (entry 12). This reaction failed completely without
any catalyst (entry 15).
Under the optimized reaction condition (i.e., 10 mol % FeCl3 in
DMF at 120 °C for 8 h, followed by 12 N HCl for 4 h at room tem-
perature) the scope of this methodology was explored with various
substrates depicted in Table 2.
This reaction worked well in case of the other precursors 1b–n
to afford the desired products 2b–n in good to excellent yield. We
have also attempted this reaction using N-(5-bromo-2-oxo-2H-
chromen-6-yl)-4-nitrobenzamide (Table 2, entry 15, 1o) and N-
(5-bromo-2-oxo-2H-chromen-6-yl)-4-hydroxybenzamide (Table 2,
entry 16, 1p), but the substrates 1o and 1p underwent extensive
decomposition and no tractable product was obtained. Perhaps
the incompatibility of the substrates with iron chloride at such
high temperature prevented the reaction.
For mechanistic study we took 1b as model substrate. A proba-
ble mechanistic rationalization for the formation of product 2b
from the substrate 1b may be formulated containing a similar
pathway as suggested by Ma et al.13 for their copper catalyzed
reaction (Scheme 1).
our delight, we were able to isolate product 3 in good yield
(72%). This unambiguously confirms the intermediacy of C in the
reaction.
Here we have described an efficient, one-pot, economic, and
high yielding method, except for the substrates incompatible with
FeCl3 at high temperature, for the synthesis of 7H-chromeno[6,5-
d]thiazol-7-one and thiazolo[5,4-f]quinolin-7(6H)-one derivatives.
Both Li and co-workers15a and Ding et al.10f described iron-cata-
lyzed synthesis of 2-amino benzothiazoles from the reaction of
2-haloanilines and aryl or alkyl isothiocyanates. Carbon–sulfur
coupling is a well-known reaction in organic synthesis but in most
of the cases organic thiols, thioureas, and thioamides are used as
the sulfur source and generally palladium and copper were used
as catalysts.16 Iron-catalyzed carbon–sulfur coupling is less inves-
tigated in the literature. Lee and co-workers17 and Bolm and co-
workers18 reported iron-catalyzed carbon–sulfur coupling but
these are limited to aryl and alkyl thiols as coupling partner and
expensive ligands were used in the coupling reaction. However,
we for the first time have used much cheaper sodium sulfide as
sulfur source and iron chloride as catalyst, under ligand-free condi-
tion, for the formation of fused thiazoles. Most of the synthesized
We tried to trap the proposed intermediate C by adding iodo-
methane in the reaction mixture prior to treatment with HCl. To

4424
K. C. Majumdar, D. Ghosh / Tetrahedron Letters 54 (2013) 4422–4424
Br
SMe
Me
N
H
H
N
Me
N
Me
S
Intramolecular
condensation
O
O
O
O
O
O
1b
3
HCl
O
O
2b
FeCl3
CH3I
Br
NaS
FeCl3
FeCl3
SNa
NaS
Br
FeCl3
H
N
H
H
Me
N
Me
N
Me
O
O
O
O
O
O
O
O
O
C
B
A
Scheme 1. Plausible mechanistic path for the formation of 2b.
5. (a) Dawood, K. M.; Gawad, H. A.; Rageb, E. A.; Ellithey, M.; Mohamed, H. A.
Bioorg. Med. Chem. 2006, 14, 3672; (b) Azam, F.; Alkskas, I. A.; Khokra, S. L.;
Prakash, O. Eur. J. Med. Chem. 2009, 44, 203.
6. (a) Shiradkar, M. R.; Murahari, K. K.; Gangadasu, H. R.; Suresh, T.; Kalyan, C. A.;
Panchal, D.; Kaur, R.; Burange, P.; Ghogare, J.; Mokalec, V.; Raut, M. Bioorg. Med.
Chem. 2007, 15, 3997; (b) Aridoss, G.; Amirthaganesan, S.; Kima, M. S.; Kim, J.
T.; Jeong, Y. T. Eur. J. Med. Chem. 2009, 44, 4199.
compounds are analogous to the compounds synthesized by Amin
et al. which showed anticonvulsant activity.9b Hence, we hope, the
synthetic protocol as well as the synthesized compounds would
become useful for the medicinal and pharmaceutical applications.
Further work on iron-catalyzed carbon–sulfur coupling is in pro-
gress and will be communicated in due course.
7. Wu, J.; Liao, Y.; Yang, Z. J. Org. Chem. 2001, 66, 3642.
8. (a) Dickinson, J. M. Nat. Prod. Rep. 1993, 10, 71; (b) Pirrung, M. C.; Blume, F. J.
Org. Chem. 1999, 64, 3642; (c) Boyd, D. R.; Sharma, N. D.; Barr, S. A.; Carroll, J. G.;
Mackerracher, D.; Malone, J. F. J. Chem. Soc., Perkin Trans. 1 2000, 3397; (d) Lee,
Y. R.; Kim, B. S.; Kweon, H. I. Tetrahedron 2000, 56, 3867; (e) Bar, G.; Parsons, A.
F.; Thomas, C. B. Tetrahedron 2001, 57, 4719.
9. (a) Kalkhambkar, R. G.; Kulkarni, G. M.; Shivkumar, H.; Rao, N. R. Eur. J. Med.
Chem. 2007, 42, 1272; (b) Amin, K. M.; Rahman, A. D. E.; Al-Eryani, Y. A. Bioorg.
Med. Chem. 2008, 16, 5377.
10. (a) Wang, J.; Peng, F.; Jiang, J.; Lu, Z.; Wang, L.; Bai, J.; Pan, Y. Tetrahedron Lett.
2008, 49, 467; (b) Saha, P.; Ramana, T.; Purkait, N.; Ali, M. A.; Paul, R.;
Punniyamurthy, T. J. Org. Chem. 2009, 74, 8719; (c) Shen, G.; Lv, X.; Bao, W. Eur.
J. Org. Chem. 2009, 5897; (d) Ding, Q.; He, X.; Wu, J. J. Comb. Chem. 2009, 11,
587; (e) Sahoo, S. K.; Jamir, L.; Guin, S.; Patel, B. K. Adv. Synth. Catal. 2010, 352,
2538; (f) Ding, Q.; Cao, B.; Liu, X.; Zong, Z.; Peng, Y.-Y. Green Chem. 2010, 12,
1607; For review see (g) Gupta, A.; Rawat, S. J. Curr. Pharm. Res. 2010, 3, 13; (h)
Inamoto, K.; Hasegawa, C.; Kawasaki, J.; Hiroya, K.; Doi, T. Adv. Synth. Catal.
2010, 352, 2643; (i) Sun, Y.-L.; Zhang, Y.; Cui, X.-H.; Wang, W. Adv. Synth. Catal.
2011, 353, 1174.
Acknowledgments
We thank DST (New Delhi), UGC (New Delhi) and CSIR (New
Delhi) for the financial assistance. K.C.M. is thankful to UGC,
(New Delhi) for UGC Emeritus Fellowship and D.G. is grateful to
CSIR, (New Delhi) for research fellowship. We also thank DST
(New Delhi) for providing Bruker NMR spectrometer (400 MHz)
and Perkin–Elmer CHN analyzer, UV–vis spectrometer and Per-
kin–Elmer FT-IR under FIST program.
Supplementary data
Supplementary data associated with this article can be found, in
11. Herrero, M. T.; Tellitu, I.; Hernández, S.; Domínguez, E.; Moreno, I.; SanMartín,
R. ARKIVOC 2002, 5, 31–37.
the
online
version,
at
http://dx.doi.org/10.1016/
j.tetlet.2013.06.017.
12. Majumdar, K. C.; De, N.; Ghosh, D.; Ponra, S.; Roy, B. Synthesis 2012, 44, 87.
13. Ma, D.; Xie, S.; Xue, P.; Zhang, X.; Dong, J.; Jiang, Y. Angew. Chem., Int. Ed. 2009,
48, 4222.
References and notes
14. For some of our recent synthesis of heterocycles, see: (a) Majumdar, K. C.;
Mondal, S.; Ghosh, D. Synthesis 2010, 7, 1176; (b) Majumdar, K. C.; Mondal, S.;
Ghosh, D.; Chattopadhyay, B. Synthesis 2010, 8, 1315; (c) Majumdar, K. C.;
Ponra, S.; Ghosh, D.; Taher, A. Synlett 2011, 104; (d) Majumdar, K. C.; Ansary, I.;
Samanta, S.; Roy, B. Tetrahedron Lett. 2011, 52, 411; (e) Majumdar, K. C.; Ghosh,
D.; Mondal, S. Synthesis 2011, 4, 599; (f) Majumdar, K. C.; Hazra, S.; Roy, B.
Tetrahedron Lett. 2011, 52, 6697; (g) Majumdar, K. C.; Nandi, R. K.; Ponra, S.
Synlett 2012, 113; (h) Majumdar, K. C.; Ganai, S.; Nandi, R. K.; Ray, K.
Tetrahedron Lett. 2012, 53, 1553.
15. (a) Qiu, J.-W.; Zhang, X.-G.; Tang, R.-Y.; Zhong, P.; Li, J.-H. Adv. Synth. Catal.
2009, 351, 2319.
16. (a) Benedí, C.; Bravo, F.; Uriz, P.; Fernández, E.; Claver, C.; Castillón, S.
Tetrahedron Lett. 2003, 44, 6073; (b) Joyce, L. L.; Evindar, G.; Batey, R. A. Chem.
Commun. 2004, 446; (c) Evindar, G.; Batey, R. A. J. Org. Chem. 2006, 71, 1802; (d)
Itoh, T.; Mase, T. Org. Lett. 2007, 18, 3687.
1. (a) Narayana, B.; Vijaya Raj, K. K.; Ashalatha, B. V.; Kumari, N. S.; Sarojini, B. K.
Eur. J. Med. Chem. 2004, 39, 867; (b) Chimenti, F.; Bizzarri, B.; Maccioni, E.; Secci,
D.; Bolasco, A.; Fioravanti, R.; Chimenti, P.; Granese, A.; Carradori, S.; Rivanera,
D.; Lilli, D.; Zicari, A.; Distinto, S. Bioorg. Med. Chem. Lett. 2007, 17, 4635.
2. (a) Palmer, P. J.; Trigg, R. B.; Warrington, J. V. J. Med. Chem. 1971, 14, 248; (b)
Vicini, P.; Geronikaki, A.; Anastasia, K.; Incerti, M.; Zani, F. Bioorg. Med. Chem.
2006, 14, 3859; (c) Dundar, O. B.; Ozgen, O.; Mentese, A.; Altanlar, N.; Ath, O.;
Kendj, E.; Ertan, R. Bioorg. Med. Chem. 2007, 15, 6012; (d) Karegoudar, P.;
Karthikeyan, M. S.; Prasad, D. J.; Mahalinga, M.; Holla, B. S.; Kumari, N. S. Eur. J.
Med. Chem. 2008, 43, 261.
3. (a) Holla, B. S.; Malini, K. V.; Rao, B. S.; Sarojini, B. K.; Kumari, N. S. Eur. J. Med.
Chem. 2003, 38, 313; (b) Kumar, A.; Rajput, C. S.; Bhati, S. K. Bioorg. Med. Chem.
2007, 15, 3089.
4. (a) Hutchinson, I.; Chua, M. S.; Browne, H. L.; Trapani, V.; Bradshaw, T. D.;
Westwell, A. D.; Stevens, M. F. G. J. Med. Chem. 2001, 44, 1446; (b) Popsavin, M.;
Spaic, S.; Svircev, M.; Kojic, V.; Bogdanovic, G.; Popsavin, V. Bioorg. Med. Chem.
Lett. 2007, 17, 4123.
17. Wu, J.-R.; Lin, C.-H.; Lee, C.-F. Chem. Commun. 2009, 4450.
18. Correa, A.; Carril, M.; Bolm, C. Angew. Chem., Int. Ed. 2008, 47, 2880.