NbCl5-catalyzed, solvent-free, one-pot synthesis of coumarins

Article abstract of DOI:10.1080/00397911.2010.486514

NbCl₅ is found to be an efficient catalyst for the Pechmann condensation reaction of phenols and -keto ester leading to the formation of coumarin derivatives in excellent yields under solvent-free conditions. The reaction protocol is simple and environmentally friendly.

Full text of DOI:10.1080/00397911.2010.486514

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NbCl5-Catalyzed, Solvent-Free, One-Pot
Synthesis of Coumarins
Shu-Tao Gao a , Chao Li a , Yanen Wang a , Jing-Jun Ma a , Chun Wang
a & Jing-Wen Zhang a
a College of Sciences, Agricultural University of Hebei , Baoding ,
China
Published online: 30 Mar 2011.
To cite this article: Shu-Tao Gao , Chao Li , Yanen Wang , Jing-Jun Ma , Chun Wang & Jing-Wen Zhang
(2011) NbCl5-Catalyzed, Solvent-Free, One-Pot Synthesis of Coumarins, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:10, 1486-1491,
DOI: 10.1080/00397911.2010.486514
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Synthetic Communications1, 41: 1486–1491, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.486514
NbCl5-CATALYZED, SOLVENT-FREE, ONE-POT
SYNTHESIS OF COUMARINS
Shu-Tao Gao, Chao Li, Yanen Wang, Jing-Jun Ma,
Chun Wang, and Jing-Wen Zhang
College of Sciences, Agricultural University of Hebei, Baoding, China
GRAPHICAL ABSTRACT
Abstract NbCl5 is found to be an efficient catalyst for the Pechmann condensation reaction
of phenols and b-keto ester leading to the formation of coumarin derivatives in excellent
yields under solvent-free conditions. The reaction protocol is simple and environmentally
friendly.
Keywords Coumarins; b-keto ester; NbCl5; Pechmann condensation; phenols;
solvent-free
INTRODUCTION
Coumarins and their derivatives are naturally occurring important plant
constituents and occupy a unique place in medicinal and synthetic organic chemistry,
as well as in materials science. They are widely used as additives in food, fragrances,
pharmaceuticals, and agrochemicals[1] and also are used as optical brightening
agents[2] and dispersed fluorescent and laser dyes.[3] Therefore, many synthetic routes
have been reported for the synthesis of coumarins including the Perkin,[4]
Pechmann,[5] Knoevenagel,[6] Reformatsky,[7] and Wittig[8] reactions and flash vac-
uum pyrolysis.[9] Among these methods, the Pechmann condensation reaction of
phenols and b-keto esters catalyzed by acidic catalyst is the most widely applied
method for the synthesis of coumarin derivatives. A lot of acid catalysts have been
used in the conventional procedure, such as H2SO4,[5] P2O5,[10a] AlCl3,[10b] polypho-
sphoric acid (PPA),[10c] TiCl4,[10d] InCl3,[10e] Sm(NO3)3,[10f] BiCl3,[10g] ZrCl4,[10h]
SnCl4 ꢀ H2O,[10i] SnCl2 ꢀ 2H2O,[10j] and WO3-ZrO2 nanocomposites.[10k] However,
many of these procedures suffer from one or more disadvantages such as long
Received February 7, 2010.
Address correspondence to Chun Wang, College of Sciences, Agricultural University of Hebei,
Baoding 071001, Hebei Province, China. E-mail: wangc69@yahoo.com.cn
1486

NbCl5-CATALYZED COUMARIN SYNTHESIS
1487
Scheme 1. The Pechmann condensation reaction of phenols and b-keto ester.
reaction time, tedious workup procedure, and poor yields and required large
amounts of catalyst, which lead to environmental pollution. Thus, a mild, efficient,
and environmentally friendly method for the synthesis of coumarins is desirable.
More recently, NbCl5 has become a research focus as a Lewis acid catalyst in
promoting various organic transformations.[11] Comparing with other Lewis acid,
niobium(V) chloride has some advantages such as ease of handling, moisture stab-
ility, and low catalyst loading.[12]
In connection with our research in developing environmentally benign
synthetic methodologies,[13] herein we report a mild and efficient condensation reac-
tion of phenols and b-keto ester catalyzed by NbCl5 under solvent-free condition
(Scheme 1).
EXPERIMENTAL
Melting points were recorded on an electrothermal apparatus and are uncor-
rected. 1H NMR (300-MHz) spectra were determined with Brucker Avance 300 spec-
trometer (CDCl3) using tetramethylsilane (TMS) as internal standard. Infrared (IR)
spectra (cmꢁ1) were measured with a WQF-510 spectrometer. Phenols, ethyl aceto-
acetate, NbCl5, and ethanol were purchased from the Beijing Chemical Reagents
Company.
General Procedure
A mixture of 10 mmol phenol 1, 10 mmol ethyl acetoacetate 2, and NbCl5
(5 mol%) was stirred at 80 ꢂC for a certain period of time (shown in Table 1) to
complete the reaction (monitored by thin-layer chromatography, TLC). After
completion, the reaction mixture was poured into cold water and filtered, and the
separated solid was washed with cold water. The crude product was recrystallized
from ethanol to afford the coumarin. All the products were fully characterized
by IR, 1H NMR spectroscopy, and melting points, which were consistent with
literature data.
Spectroscopic Data for Compounds
Entry 3a. 1H NMR (300 MHz, CDCl3): d 7.50 (d, J ¼ 8.7 Hz, 1H), 6.91 (s, 1H),
6.82 (d, J ¼ 8.7 Hz, 1H), 6.15 (s, 1H), 2.41 (s, 3H); IR (KBr): 3448, 3030, 1685, 1590,
1265, 1065 cmꢁ1
.
Entry 3b. 1H NMR (300 MHz, CDCl3): d 6.24 (s, 1H), 6.15 (s, 1H), 5.80
(s, 1H), 2.55 (s, 3H); IR (KBr): 3395, 3020, 1698, 1585, 1232, 1065 cmꢁ1
.

1488
S.-T. GAO ET AL.
Table 1. Pechmann condensation reactions of phenols and ethyl acetoacetate catalyzed by NbCl5
Entry
a
Phenols
Products
Time (min)
15
Yield (%)
94
Mp (ꢂC)
183–185
Mp[lit.] (ꢂC)
185[14]
b
c
15
20
96
82
280–282
242–244
280–285[14]
241–243[10h]
d
e
25
20
85
87
130–131
160–162
131–132[10d]
161–162[15]
f
25
78
154–155
155–156[14]
g
25
25
70
78
79–81
82[15]
h
221–223
220–224[16]
Entry 3c. 1H NMR (300 MHz, CDCl3): d 6.89–7.22 (m, 2H), 6.10 (s, 1H), 2.40
(s, 3H); OH not observed. IR (KBr): 3415, 3230, 1652, 1956, 1190, 1062 cmꢁ1
.
Entry 3d. 1H NMR (300 MHz, CDCl3): d 7.10–7.62 (m, 3H), 6.38 (s, 1H) 2.81
(s, 3H), 2.60 (s, 3H); IR (KBr): 3054, 1685, 1210, 1065 cmꢁ1
.
Entry 3e. 1H NMR (300 MHz, CDCl3): d 7.50 (d, J ¼ 8.7 Hz, 1H), 6.87
(d, J ¼ 8.7 Hz, 1H), 6.82 (s, 1H), 6.06 (s, 1H), 3.83 (s, 3H), 2.40 (s, 3H); IR (KBr):
3045, 1680, 1566, 1215, 1078 cmꢁ1
.
Entry 3f. 1H NMR (300 MHz, CDCl3): d 8.58 (d, J ¼ 9.0 Hz, 1H), 7.86
(d, J ¼ 9.0 Hz, 1H), 7.45–7.70 (m, 4H), 6.40 (s, 1H), 2.54 (s, 3H); IR (KBr): 3020,
1715, 1578, 1245, 1044 cmꢁ1
.
Entry 3g. 1H NMR (300 MHz, CDCl3): d 7.46 (d, J ¼ 6.0 Hz, 1H), 7.12–7.40
(m, 3H), 6.28 (s, 1H), 2.40 (s, 3H); IR (KBr): 3025, 1715, 1533, 1248, 1060 cmꢁ1
.
Entry 3h. 1H NMR (300 MHz, CDCl3): 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 (s, 1H), 2.30 (s, 3H); IR (KBr): 3468, 3312,
3012, 1688, 1570, 1238, 1052 cmꢁ1
.

NbCl5-CATALYZED COUMARIN SYNTHESIS
1489
RESULTS AND DISCUSSION
To study the feasibility of the NbCl5-catalyzed Pechmann condensation, the
reaction of resorcinol with ethyl acetoacetate was selected as a model. The results
indicated that only 5 mol% of NbCl5 could effectively catalyze the reaction, which
could be completed in 15 min at 80 ꢂC under solvent-free conditions. No product
was obtained in the absence of NbCl5 catalyst, thus highlighting the role of the NbCl5
as a promoter. Comparing with other Lewis acids, niobium(V) chloride has some
advantages such as ease of handling, moisture stability, and low catalyst loading.[12]
Any excess of NbCl5 beyond this loading did not show any substantial improvement
in the yield. So 5 mol % NbCl5 was chosen as the optimal loading of the catalyst.
To generalize the proposed method, a series of monohydric and polyhydric
phenols were subjected to react with ethyl acetoacetate to obtain the corresponding
substituted coumarins (Table 1). The results indicated that a wide range of structur-
ally varied phenols reacted smoothly to give the coumarins in good yields. It is worth
mentioning that substrates such as phenol, aminophenol, and cresols, which failed to
react in some of the reported documents, showed better reactivity under the reaction
conditions.
In conclusion, we have developed a simple, rapid, and environmentally benign
method for the synthesis of coumarins using NbCl5 as catalyst under solvent-free
conditions. The advantages of this protocol are good yields, short reaction time,
and low catalyst loading. We believe that this method could be a valuable alternative
to the present methodologies for the synthesis of coumarins.
ACKNOWLEDGMENTS
This work was financially supported by the Natural Science Foundation of
Hebei (B2011204051), the Scientific Research Foundation of Education Department
of Hebei Province (2010137), and the Natural Science Foundation of the Agricul-
tural University of Hebei (2009-001).
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