Gallium triiodide-catalyzed organic reaction: A convenient procedure for the synthesis of coumarins

Article abstract of DOI:10.1081/SCC-200064906

Gallium triiodide, which was generated in situ by the reaction of gallium metal and iodine, was used as an efficient catalyst in the Pechmann condensation of phenols with ethyl acetoacetate, leading to the formation of coumarins. The reaction proceeded in dichloromethane at room temperature with good to excellent yields. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200064906

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Gallium Triiodide–Catalyzed
Organic Reaction: A
Convenient Procedure for the
Synthesis of Coumarins
a
a
Peipei Sun & Zhixin Hu
a
College of Chemistry and Environmental Science ,
Nanjing Normal University , Nanjing, China
Published online: 16 Aug 2006.
To cite this article: Peipei Sun & Zhixin Hu (2005) Gallium Triiodide–Catalyzed
Organic Reaction: A Convenient Procedure for the Synthesis of Coumarins, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 35:14, 1875-1880, DOI: 10.1081/SCC-200064906
To link to this article: http://dx.doi.org/10.1081/SCC-200064906
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Synthetic Communications , 35: 1875–1880, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200064906
Gallium Triiodide–Catalyzed Organic
Reaction: A Convenient Procedure for
the Synthesis of Coumarins
Peipei Sun and Zhixin Hu
College of Chemistry and Environmental Science, Nanjing Normal
University, Nanjing, China
Abstract: Gallium triiodide, which was generated in situ by the reaction of gallium
metal and iodine, was used as an efficient catalyst in the Pechmann condensation of
phenols with ethyl acetoacetate, leading to the formation of coumarins. The reaction
proceeded in dichloromethane at room temperature with good to excellent yields.
Keywords: Coumarins, ethyl acetoacetate, gallium triiodide, Pechmann reaction,
phenols
INTRODUCTION
Coumarins are a very important group of organic compounds not only in
organic synthesis but also in biology and food, as well as in materials
[1]
science. For example, they can be used as additives to food and cosmetics
or fluorescent materials in optical devices, that is, in organic light-emitting
[2]
[3]
diodes and molecular photonic devices. Therefore, the synthesis of
coumarins and their derivatives has attracted considerable attention from
chemists. Among numerous methods, the Pechmann reaction is an
important approach. 4-Substituted coumarins can be synthesized simply by
the condensation of substituted phenols with b-ketoesters in an acidic
[4]
medium. Traditional Pechmann reaction was catalyzed by acidic reagents
Received in Japan January 11, 2005
Address correspondence to Peipei Sun, College of Chemistry and Environmental
Science, Nanjing Normal University, Nanjing 210097, China. E-mail: sunpeipei@
njnu.edu.cn
1
875

1876
P. Sun and Z. Hu
[
5]
such as H SO , HCl, CF COOH, and so forth. It might also be catalyzed by
2
4
3
[
6]
some solid acids. In these methods, long reaction times or high reaction
temperatures, (above 1508C), were needed, which depended on their reactiv-
ity. In some cases, undesired side products such as chromones were also
generated in addition to coumarins. Moreover, the disposal of excess acid
waste might lead to environmental pollution. In recent years, Lewis acids
such as InCl , AlCl -nBPC, Yb(OTf) , ZrCl , and Sm(NO ) as well as
3
3
3
4
3 3
[7]
acidic ionic liquid were employed to catalyze Pechmann reactions.
However, some of these Lewis acids are moisture sensitive and require
special care in handling and storage, and some of these methods still need a
high reaction temperature or a long reaction time. Furthermore, metal
triflates are highly expensive.
In the course of our recent work on Lewis acid–catalyzed organic
reactions, we have found that gallium triiodide has emerged as a powerful
Lewis acid catalyst in some reactions such as the Sakurai reaction, the tetra-
hydropyranylation of alcohols and phenols, and the coupling reaction of
[8]
carbonyl compounds, amines, and diethyl phosphite. Another evident
advantage of this reagent is that it can be prepared in situ by a simple
inorganic reaction of gallium with iodine, which can bring some advantages
for its application. We suppose that it will have a great potential to be used
in organic synthesis. Here, we report the use of gallium triiodide in a con-
venient synthesis of coumarins by the Pechmann reaction.
4
-Methylcoumarins were synthesized by the reaction of phenols and ethyl
acetoacetate under the catalysis of gallium triiodide (Scheme 1) in dichloro-
methane. The results are summarized in Table 1. The Lewis acid catalyst,
gallium triiodide, was generated easily in situ by the reaction of gallium
metal and iodine, and a small excess of either Ga or I did not make any differ-
2
ence to the normal course of reaction. It showed that GaI exhibited a powerful
3
catalytic activity in an amount as low as 10 mol%, which was enough to
complete the reaction at room temperature within a few hours for most of
the substrates we used, and a larger amount of catalyst or higher reaction
temperature (under reflux) could not enhance the rates or increase the yields
evidently. Dichloromethane was found to be the effective solvent for this con-
version. The catalyst could dissolve in it to form a homogeneous solution, and
thus the strong electrostatic activation to the substrates made the reaction take
Scheme 1.

Gallium Triiodide-Catalyzed Reaction
1877
Table 1. GaI
3
-catalyzed Pechmann reaction
Substrate
a
Time
(h)
Yield
(%)
Entry
1
Product
0.7
96
2
3
1
90
94
1
4
5
1.5
1.2
86
85
6
7
2
2.5
10
83
80
b
65
8
a
1
Isolated yields. The products were characterized by HNMR and IR spectra analysis
and comparison of their mp with the reports.
b
Under reflux.

1878
P. Sun and Z. Hu
place smoothly. Commercial dichloromethane could be used directly and
further purification was not needed. The method was adaptive to the substrates
with electron-donating groups, and the reaction gave good to excellent yields
in a short time. With unsubstituted phenol, it proceeded slower and mode-
rate yields were given even under reflux for as long as 10 h (Entry 8). To
the substrates with electron-withdrawing groups such as p-chlorophenol, the
reaction was very sluggish and only a trace product was generated after it
reacted for 24 h.
In summary, we have developed a new and efficient procedure for a
Pechmann reaction catalyzed by GaI . The method offers several advantages
3
such as mild reaction conditions, short reaction times, high yields, and a
simple experimental operation, leading to a useful and attractive process for
the preparation of coumarins. It is also revealed that GaI is an effective
3
and useful Lewis acid catalyst. Its further application in organic synthesis is
currently being explored in our laboratory.
EXPERIMENTAL
General Procedure for the Synthesis of Coumarins
Gallium metal (0.1 mmol) and iodine (0.15 mmol) were added to 2 mL of
dichloromethane. The mixture was stirred and refluxed under nitrogen atmos-
phere until the reaction was complete (the reactants disappeared; it needed
about 0.5 h), then cooled to room temperature. To this solution was added
phenol (1.0 mmol) and ethyl acetoacetate (1.0 mmol). The resulting mixture
was stirred at room temperature for an appropriate time (see Table 1,
monitored by TLC) and quenched with water. The mixture was then
extracted with CH Cl or ethyl acetate and purified by column chromatography
2
2
on silica gel with hexane/ethyl acetate (2:1) as eluent to yield the product.
[7b]
[7b]
1
2
a
: mp: 185–1878C (lit.
182–1848C); H NMR (300 MHz,
CDCl ): d 7.51 (d, J ¼ 8.7 Hz, 1H), 6.93 (s, 1H), 6.85 (d, J ¼ 8.7 Hz, 1H),
3
6
1
.17 (s, 1H), 2.43 (s, 3H); IR (KBr): 3445, 3034, 1686, 1587, 1260,
075 cm
2
1
.
[
9]
[9]
1
2
b : mp: 160–1628C (lit. 158–1598C); H NMR (300 MHz, CDCl ):
3
d 7.52 (d, J ¼ 8.7 Hz, 1H), 6.88 (d, J ¼ 8.7 Hz, 1H), 6.85 (s, 1H), 6.16 (s, 1H),
2
1
3
.85 (s, 3H), 2.42 (s, 3H); IR (KBr): 3052, 1690, 1568, 1215, 1088 cm
.
[7b]
[7b]
1
2 : mp: 282–2848C (lit. 284–2858C); H NMR (300 MHz, DMSO-
d ): d 6.26 (s, 1H), 6.17 (s, 1H), 5.85 (s, 1H), 2.50 (s, 3H); IR (KBr): 3385,
c
6
2
1
.
[5d]
3
024, 1703, 1587, 1232, 1064 cm
2
[5d]
1
d
: mp: 240–2428C (lit.
241–2428C); H NMR (300 MHz,
DMSO-d ): d 7.05 (s, 1H), 6.74 (d, J ¼ 8.4 Hz, 1H), 6.72 (d, J ¼ 8.4 Hz,
6
1
1
H), 6.33 (s, 1H), 2.42 (s, 3H); IR (KBr): 3412, 3010, 1693, 1565, 1225,
055 cm
2
1
.

Gallium Triiodide-Catalyzed Reaction
1879
[10]
[10]
1
2
e
: mp: 220–2228C (lit. 220–2248C); H NMR (300 MHz, DMSO-
d ): d 7.40 (d, J ¼ 8.7 Hz, 1H), 6.55 (d, J ¼ 8.7 Hz, 1H), 6.40 (s, 1H), 5.90
6
(
s, 1H), 2.30 (s, 3H); IR (KBr): 3468, 3312, 3012, 1688, 1570, 1238,
052 cm
2
1
1
.
[
5d]
[5d]
1
2
f
: mp: 153–1548C (lit.
1558C); H NMR (300 MHz, CDCl ):
3
d 8.60 (d, J ¼ 9.0 Hz, 1H), 7.89 (d, J ¼ 9.0 Hz, 1H), 7.48–7.70 (m, 4H),
2
1
6
.41 (s, 1H), 2.56 (s, 3H); IR (KBr): 3010, 1708, 1575, 1238, 1046 cm
g
.
[11]
[11]
1
2
: mp: 177–1798C (lit. 180.5–181); H NMR (300 MHz, CDCl ):
3
d 8.63 (d, J ¼ 8.7 Hz, 1H), 8.00 (d, J ¼ 9.0 Hz, 1H), 7.94 (d, J ¼ 8.7 Hz, 1H),
7
.55–7.68 (m, 2H), 7.51 (d, J ¼ 9.0 Hz, 1H), 6.42 (s, 1H), 2.97 (s, 3H); IR
2
1
(
KBr): 3024, 1702, 1568, 1242, 1038 cm
2
.
[9]
[9]
1
h : mp: 79–808C (lit. 828C); H NMR (300 MHz, CDCl ): d 7.48
3
(
d, J ¼ 6.0 Hz, 1H), 7.15–7.42 (m, 3H), 6.32 (s, 1H), 2.42 (s, 3H); IR
2
1
(
KBr): 3020, 1705, 1543, 1238, 1064 cm
.
ACKNOWLEDGMENT
Financial support of this research from the Natural Science Foundation of the
Education Department of Jiangsu Province is gratefully acknowledged
(
Project 03KJD150109).
REFERENCES
1
2
3
. Kennedy, R. O.; Thornes, R. D. Coumarins: Biology, Applications and Mode of
Action; Wiley and Sons: Chichester, 1997.
. Mitsuya, M.; Suzuki, T.; Koyama, T. Bright red organic light-emitting diodes
doped with a fluorescent dye. Appl. Phys. Lett. 2000, 77, 3272.
. Adronov, A.; Gilat, S. L.; Frechet, J. M. J.; Ohta, K.; Neuwahl, F. V. R.;
Fleming, G. R. Light harvesting and energy transfer in laser-dye-labeled
poly(aryl ether) dendrimers. J. Am. Chem. Soc. 2000, 122, 1175.
4
. (a) Pechmann, H. V.; Duisberg, C. Ueber die Verbindungen der Phenole mit
Acetessig a¨ ther. Ber. Dtsch. Chem. Ges. 1883, 16, 2119; (b) Sethna, S.;
Phadke, R. The Pechmann reactions. Org. React. (N.Y.) 1953, 7, 1.
5
. (a) Robertson, A.; Sandrock, W. F.; Henry, C. B. Hydroxy-carbonyl compounds.
Part V. The preparation of coumarins and 1:4-pyrones from phenol, p-cresol,
quinol and a-naphthol. J. Chem. Soc. 1931, 2426; (b) Appel, H. An improved
method for the synthesis of coumarins by v. Pechmann’s method. J. Chem. Soc.
1935, 1031; (c) Woods, L. L.; Sapp, J. A new one-step synthesis of substituted
coumarins. J. Org. Chem. 1962, 27, 3703; (d) Singh, V.; Singh, J.; Kaur, K. P.;
Kad, G. L. Acceleration of the Pechmann reaction by microwave irradiation:
Application to the preparation of coumarins. J. Chem. Res., Synop. 1997, 58.
. (a) Hoefnagel, A. J.; Gennewagh, E. A.; Downing, R. S.; Bekkum, H. V. Synthesis
of 7-hydroxycoumarins catalysed by solid acid catalysts. J. Chem. Soc., Chem.
Commun. 1995, 225; (b) de la Hoz, A.; Moreno, A.; Vazquez, E. Use of
microwave irradiation and solid acid catalysts in an enhanced and environmentally
6

1880
P. Sun and Z. Hu
friendly synthesis of coumarin derivatives. Synlett 1999, 608; (c) Romanelli, G. P.;
Bennardi, D.; Ruiz, D. M.; Baronetti, G.; Thomas, H. J.; Autino, J. C. A solvent-
free synthesis of coumarins using a Wells–Dawson heteropolyacid as catalyst.
Tetrahedron Lett. 2004, 45, 8935; (d) Singh, P. R.; Singh, D. U.; Samant, S. D.
Sulfamic acid—an efficient and cost-effective solid acid catalyst for the
Pechmann reaction. Synlett 2004, 1909.
7. (a) Bose, D. S.; Rudradas, A. P.; Babu, M. H. The indium(III) chloride-catalyzed
von Pechmann reaction: A simple and effective procedure for the synthesis of
4
-substituted coumarins. Tetrahedron Lett. 2002, 43, 9195; (b) Khandekar, A. C.;
Khadilkar, B. M. Pechmann reaction in chloroaluminate ionic liquid. Synlett
002, 152; (c) Wang, L. M.; Xia, J. J.; Tian, H.; Qian, C. T.; Ma, Y. Synthesis of
coumarin by Yb(OTf) -catalyzed Pechmann reaction under the solvent-free
conditions. Indian J. Chem. B 2003, 42, 2097; (d) Smitha, G.; Reddy, C. S.
ZrCl -catalyzed Pechmann reaction: Synthesis of coumarins under solvent-free
conditions. Synth. Commun. 2004, 34, 3997; (e) Gangadasu, B.; Narender, P.;
Raju, B. C.; Rao, V. J. ZrCl -catalyzed solvent-free synthesis of coumarins.
2
3
4
4
J. Chem. Res. 2004, 480; (f) Bahekar, S. S.; Shinde, D. B. Samarium(III)-
catalyzed one-pot construction of coumarins. Tetrahedron Lett. 2004, 45, 7999;
(
g) Singh, V.; Kaur, S.; Sapehiyia, V.; Singh, J.; Kad, G. L. Microwave-accelerated
preparation of [bmim][HSO ] ionic liquid. An acid catalyst for improved synthesis
4
of coumarins. Catal. Commun. 2005, 6, 57.
3
8. (a) Sun, P. P.; Xian, Y. F.; Xiao, Y. P. GaI -catalyzed nucleophilic addition of
allyltrimethylsilane to aldehydes. J. Chem. Res. 2004, 216; (b) Sun, P. P.;
Hu, Z. X. GaI -catalyzed tetrahydropyranylation of alcohols and phenols. Chin.
3
J. Chem. 2004, 22, 1341; (c) Sun, P. P.; Hu, Z. X.; Huang, Z. H. Gallium
Triiodide–catalyzed organic reaction: A convenient synthesis of a–amino
phosphonates. Synth. Commun. 2004, 34, 4293.
9
. Mali, R. S.; Yadav, V. J. Convenient synthesis of naturally occurring coumarins,
(2-oxo-2H-benzopyrans) and 4-methylcoumarins (4-methyl-2-oxo-2H-benzopyrans).
Synthesis 1977, 464.
1
1
0. Atkins, R. L.; Bliss, D. E. Substituted coumarins and azacoumarins. Synthesis and
fluorescent properties. J. Org. Chem. 1978, 43, 1975.
1. Nagasawa, K.; Kanbara, H.; Matsushita, K.; Ito, K. A novel and efficient synthesis
of 5-substituted and 5,6-disubstituted 4-methylcoumarins using organocerium(III)
reagents. Tetrahedron Lett. 1985, 26, 6477.