Alum (KAl(SO4)2·12H2O) catalyzed one-pot synthesis of coumarins under solvent-free conditions

Article abstract of DOI:10.1007/s00706-007-0666-6

Alum (KAl(SO₄)₂·12H₂O) is used as an efficient catalyst in the Pechmann condensation of phenol derivatives with β-keto esters leading to the formation of coumarins in excellent yields under solvent-free conditions. This methodology offers significant improvements for the synthesis of coumarins with regard to the yield of products, simplicity in operation, and green aspects by avoiding toxic catalysts and solvents.

Full text of DOI:10.1007/s00706-007-0666-6

Monatshefte f u¨ r Chemie 138, 997–999 (2007)
DOI 10.1007/s00706-007-0666-6
Printed in The Netherlands
Alum (KAl(SO ) 12H O) Catalyzed One-Pot Synthesis of Coumarins
under Solvent-Free Conditions
4
2
ꢀ
Minoo Dabiri , Mostafa Baghbanzadeh, Shadi Kiani, and Yasamin Vakilzadeh
2
ꢁ
Department of Chemistry, Faculty of Science, Shahid Beheshti University, Evin, Tehran, Iran
Received February 11, 2007; accepted (revised) February 14, 2007; published online July 20, 2007
#
Springer-Verlag 2007
Summary. Alum (KAl(SO ) ꢀ 12H O) is used as an efficient
4
2
2
POCl , AlCl , PPA, HCl, phosphoric acid, and tri-
3 3
catalyst in the Pechmann condensation of phenol derivatives
with ꢀ-keto esters leading to the formation of coumarins in
excellent yields under solvent-free conditions. This methodol-
ogy offers significant improvements for the synthesis of cou-
marins with regard to the yield of products, simplicity in
operation, and green aspects by avoiding toxic catalysts and
solvents.
fluoroacetic acid are used to effect this condensation
9]. However, in the current context of environmen-
[
tal impact, these methods are not attractive as they
require catalysts in excess, for example, sulfuric acid
in 10–12 equivalents [10], trifluoroacetic acid in 3–4
equivalents [11], and P O in 5-fold excess [12].
2
5
Keywords. Heterocycle; Pechmann condensation; Coumar-
ins; Solvent-free, Alum.
Further, such reactions require long reaction times
and in some cases gave low yields. The present drive
therefore is towards the development of more effec-
tive, non-stoichiometric, preferably heterogeneous
catalysts. To overcome these problems some envi-
ronmentally benign procedures have been reported,
such as using solid supports [13], ionic liquids [14],
and solid Lewis acids [15]. KAl(SO ) ꢀ 12H O (alum)
Introduction
Coumarin and its derivatives form an important class
of benzopyrones found in Nature. They are a struc-
tural subunit in many complex natural products and
have shown various biological activities, such as an-
titumor [1], anti-HIV [2], antioxidation [3], tumor
necrosis factor-a (TNF-a) inhibition [4], antimicro-
bial activity [5], serine protease inhibition [6], and
anticancer activity [7]. The widespread biologi-
cal activities of coumarin derivatives have aroused
great interest in the area of synthesis chemistry and
pharmacology.
The Pechmann reaction is a most commonly used
method for the preparation of coumarins [8]. The
reaction involves condensation of very simple start-
ing materials i.e. phenols and ꢀ-keto esters in the
presence of a variety of acidic condensing agents.
4
2
2
with mild acidity, involatility, and incorrositivity, is
insoluble in common organic solvents and was used
recently as an easily available acidic catalyst in dif-
ferent reactions [16].
Results and Discussion
In continuation of our interest in using solid acidic
catalysts in organic reactions [17], here we wish to
report an efficient and environmentally benign pro-
cedure for the synthesis of coumarins via Pechmann
condensation in the presence of catalytic amounts
of alum. For optimizing the reaction conditions,
the reaction of resorcinol with ethyl acetoacetate in
the presence of alum at different temperatures was
investigated. The best results were obtained with
Various reagents like H SO , P O , FeCl , ZnCl ,
2
4
2
5
3
2
ꢁ Corresponding author. E-mail: m-dabiri@sbu.ac.ir

9
98
M. Dabiri et al.
Scheme 1
Table 1. Synthesis of coumarins by the reaction of phenols with ꢀ-ketoesters in the presence of 40 mol% of alum
a
Entry
Phenol
ꢀ-Ketoester
Product
Time=h
Yield=%
Ref.
O
O
1
3
80
[15e]
[15a]
Me
2
2
92
3
4
2
3
91
86
[15d]
[15a]
5
6
7
3
88
[14a]
2
90
90
[15a]
[15d]
2.5
8
9
3
2
90
91
[15a]
[15d]
1
1
0
1
2
3
95
87
[15d]
[15d]
1
2
3
81
[14a]
a
The products were characterized by comparison of their spectroscopic and physical data with authentic samples synthesized by
reported procedures

One-Pot Synthesis of Coumarins
999
ꢂ
Mazumder A, Wang SM, Sunder S, Milne GWA,
Pommier Y, Burke TB (1997) J Med Chem 40: 242
3] Yun BS, Lee IK, Ryoo IJ, Yoo ID (2001) J Nat Prod 64:
4
0mol% of alum at 80 C (92% yield). Encouraged
by the above results, other coumarin derivatives were
synthesised under the same conditions (Scheme 1).
Several types of phenolic substrates and ꢀ-keto
esters with different functionalities were used in the
reaction. As can be seen in Table 1, the reaction was
found to be adaptable to a variety of substrates and
the yields, in general, were very high (80–95%). The
experimental procedure is very simple and work-
[
[
1
238
4] a) Cheng JF, Ishikawa A, Ono Y, Arrhenius T, Nadzan A
(2003) Bioorg Med Chem 13: 3647; b) Cheng JF, Chen
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[
[
5] Zaha AA, Hazem A (2002) Microbiologica 25: 213
6] Whittaker M, Floyd CD, Brown P, Gearing AJH (1999)
Chem Rev 99: 2735
up includes the addition of H O followed by filtra-
2
tion. Hence there will not be any unnecessary acidic
waste stream to create environmentally hazardous
pollution.
In conclusion, we developed an efficient and sim-
ple alternative for the preparation of substituted cou-
marins via the alum-catalyzed Pechmann reaction
under solvent-free conditions. Prominent among the
advantages of this new method are operational sim-
plicity, good yields, short reaction times, and an easy
work-up procedure.
[7] Maly DJ, Leonetti F, Backes BJ, Dauber DS, Harris JL,
Craik CS, Ellman JA (2002) J Org Chem 67: 910
[8] Sethna SM, Phadke R (1953) Org React 7: 1
[9] a) Appel H (1935) J Chem Soc 1031; b) Woods LL, Sapp
J (1962) J Org Chem 27: 3703; c) Ahmad ZS, Desai RD
(1937) Proc Indian Acad Sci Chem Sci 5A: 277; d)
Robinson R, Weygand F (1941) J Chem Soc 386; e)
Nadkarni AJ, Kudav NA (1981) Ind J Chem Sect B 20:
7
19
[
[
[
10] Russell A, Frye JR (1941) Org Synth 21: 22
11] Woods LL, Sapp J (1962) J Org Chem 27: 3703
12] a) Simmonis H, Remmert P (1914) Chem Ber 47: 2229;
b) Robertson A, Sandrock WF, Henry CB (1931) J Chem
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13] a) Reddy BM, Patil MK, Lakahmanan P (2006) J
Mol Catal A Chem 256: 290; b) Rodriguez-Dominguez
JC, Kirsch G (2006) Tetrahedron Lett 47: 3279;
c) Maheswara M, Siddaiah V, Damu GLV, Rao YK,
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[14] a) Khandekar AC, Khadilkar BM (2002) Synlett 152;
b) Potdar MK, Rasalkar MS, Mohile SS, Salunkhe MM
(2005) J Mol Catal A Chem 233: 249
[15] a) Rodriguez-Dominguez JC, Kirsch G (2006) Synthesis
1895; b) Valizadeh H, Shockravi A (2005) Tetrahedron
Lett 46: 3501; c) De SK, Gibbs RA (2005) Synthesis
1231; d) Sharma GVM, Reddy JJ, Lakshmi PS, Krishna
PR (2005) Tetrahedron Lett 46: 6119; e) Bahekar SS,
Shinde DB (2004) Tetraheron Lett 45: 7999
Experimental
[
Melting points were measured on an Electrothermal 9200
apparatus. IR spectra were recorded on a FT-IR 102MB
BOMEM apparatus. Mass spectra were recorded on a FINNI-
GAN-MAT 8430 mass spectrometer operating at an ionization
1
13
potential of 70 eV. H and C NMR spectra were recorded on
a BRUKER DRX-300 AVANCE spectrometer at 300.13 and
7
5.47 MHz. All the products are known compounds, which
1
13
were characterized by melting point, IR, H and C NMR
spectral data, and mass spectroscopy.
General Procedure for the Synthesis of Coumarins
Phenolic substrate (1mmol), 1 mmol ꢀ-keto ester, and
0
.4 mmol alum were mixed together in a round bottom flask.
ꢂ
The mixture was stirred at 80 C for the appropriate time (see
Table 1). After completion of the reaction as indicated by TLC
[16] Dabiri M, Salehi P, Otokesh S, Baghbanzadeh M,
Kozehgary Gh, Mohammadi AA (2005) Tetrahedron
Lett 46: 6123
(
eluent: n-hexane=ethyl acetate ¼ 2=1), H O was added to the
2
mixture and it was filtered. The crude product was recrystal-
lized from ethanol.
[17] a) Dabiri M, Salehi P, Mohammadi AA, Baghbanzadeh
M (2005) Synth Commun 35: 279; b) Salehi P, Dabiri
M, Baghbanzadeh M, Bahramnejad M (2006) Synth
Commun 36: 2287; c) Dabiri M, Salehi P, Mohammadi
AA, Baghbanzadeh M, Kozehgiry G (2004) J Chem
Res (S) 570; d) Salehi P, Dabiri M, Zolfigol MA,
Bodaghi Fard MA (2003) Tetrahdron Lett 44: 2889;
e) Salehi P, Dabiri M, Zolfigol MA, Baghbanzadeh M
Acknowledgement
Financial support by the Research Council of Shahid Beheshti
University is gratefully acknowledged.
(
2005) Synlett 1155; f) Salehi P, Dabiri M, Khosropour
AR, Roozbehniya P (2006) J Iran Chem Soc 3: 98;
g) Salehi P, Dabiri M, Zolfigol MA, Bodaghi Fard MA
(2003) Heterocycles 60: 2435; h) Salehi P, Dabiri M,
Zolfigol MA, Baghbanzadeh M (2005) Tetrahedron
Lett 46: 7051; i) Salehi P, Dabiri M, Zolfigol MA,
Otokesh S, Baghbanzadeh M (2006) Tetrahedron Lett
47: 2557; j) Baghbanzadeh M, Salehi P, Dabiri M,
Kozehgary Gh (2006) Synthesis 344
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