Ceric ammonium nitrate (CAN): An efficient catalyst for the coumarin synthesis via Pechmann condensation using conventional heating and microwave irradiation

Article abstract of DOI:10.1080/00397910802029091

An efficient and convenient method for the synthesis of substituted coumarins via Pechmann condensation of different phenols with ethylacetoacetate in the presence of ammonium cerium(IV) nitrate as the catalyst in a solvent- free media using both conventional heating and microwave irradiation. Copyright Taylor & Francis Group, LLC.

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Ceric Ammonium Nitrate
(CAN): An Efficient Catalyst
for the Coumarin Synthesis
via Pechmann Condensation
using Conventional Heating and
Microwave Irradiation
Y. Thirupathi Reddy a , Vijayakumar N. Sonar a ,
Peter A. Crooks a , Pavan K. Dasari a , P. Narsimha
Reddy b & B. Rajitha b
a Department of Pharmaceutical Sciences, College
of Pharmacy, University of Kentucky, Lexington,
Kentucky, USA
b Department of Chemistry, National Institute of
Technology, Warangal, India
Published online: 18 Aug 2008.
To cite this article: Y. Thirupathi Reddy , Vijayakumar N. Sonar , Peter A. Crooks ,
Pavan K. Dasari , P. Narsimha Reddy & B. Rajitha (2008): Ceric Ammonium Nitrate
(CAN): An Efficient Catalyst for the Coumarin Synthesis via Pechmann Condensation
using Conventional Heating and Microwave Irradiation, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:13,
2082-2088
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Synthetic Communications1, 38: 2082–2088, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802029091
Ceric Ammonium Nitrate (CAN): An Efficient
Catalyst for the Coumarin Synthesis via
Pechmann Condensation using Conventional
Heating and Microwave Irradiation
Y. Thirupathi Reddy,1 Vijayakumar N. Sonar,1 Peter A. Crooks,1
Pavan K. Dasari,1 P. Narsimha Reddy2, and B. Rajitha2
1Department of Pharmaceutical Sciences, College of Pharmacy,
University of Kentucky, Lexington, Kentucky, USA
2Department of Chemistry, National Institute of Technology, Warangal, India
Abstract: An efficient and convenient method for the synthesis of substituted
coumarins via Pechmann condensation of different phenols with ethylacetoace-
tate in the presence of ammonium cerium(IV) nitrate as the catalyst in a solvent-
free media using both conventional heating and microwave irradiation.
Keywords: Ceric ammonium nitrate (CAN), Coumarins, b-ketoesters, Pechmann
condensation
INTRODUCTION
Coumarins and chromones are naturally occurring important plant con-
stituents and occupy a unique place in natural and synthetic organic
chemistry. Coumarin derivatives have a wide range of biological and
therapeutic properties such as anthelmintic, anticoagulant, hypnotic,
and insecticide properties.[1] Furthermore, they are used as additives in
food, perfumes, cosmetics, and pharmaceuticals,[1] optical brighteners,[2]
and dispersed fluorescent and laser dyes.[3] Some polycyclic coumarins
such as calanolides,[4] isolated from Calophyllum genus, and others[5] have
Address correspondence to B. Rajitha, Department of Chemistry, National
Institute of Technology, Warangal, India. E-mail: rajitabhargavi@yahoo.com
2082

Ceric Ammonium Nitrate
2083
Scheme 1.
shown potent anti-HIV activity. Coumarins are prepared by different
reactions such as the Pechmann reaction,[6] Knoevenagel reaction,[7]
and Wittig reaction.[8] The Pechmann reaction is the most common, a
two-component coupling reaction of phenol and b-keto ester in the pres-
ence of sulfuric acid as a cyclizing agent.
The reaction can also be catalyzed by different Brønsted and Lewis
acids, such as PPA,[9] InCl3,[10] ZrCl4,[11] Yb(OTf)3,[12] p-TsOH,[13]
BiCl3,[14] and I2 or AgOTf.[15] Because of recent efforts toward green
chemistry, attempts are being made to replace stoichiometric Brønsted
and Lewis acids by nonstoichiometric solid acids, such as montmorillon-
ite clay[16] and cation-exchanged resin.[17] Application of ionic liquids was
also reported.[18]
Even though various procedures are reported, disadvantages (includ-
ing low yields, prolonged reaction times, use of an excess of reagents=
catalysts, and use of toxic solvents) necessitate the development of an
alternative for the synthesis of coumarin derivatives.
Recently, ceric ammounium nitrate (CAN) has emerged as a pro-
mising solid acid catalyst for various chemical transformations.[19] In
continuation of our work[20] on the development of new synthetic meth-
odologies using acid catalysts and microwave irradiation, we have
observed that CAN is an efficient catalyst for the condensation of phe-
nol with b-ketoester in solvent-free media under conventional heating
and microwave irradiation (Scheme 1).
RESULTS AND DISCUSSION
In the conventional procedure (method A), phenol was heated with b-
ketoester at 110 ꢀC under solvent-free conditions in the presence of
CAN to afford the corresponding coumarin in 10–15 min. As part of
our ongoing work with microwave irradiation,[20] phenol was irradiated
with b-ketoester under solvent-free conditions in the presence of CAN
in a microwave oven (method B) to yield the desired coumarin in
2–3 min (Table 1).

2084
Y. T. Reddy et al.
Table 1. Ceric ammonium nitrate (CAN)–catalyzed Pechmann synthesis of
coumarins
Mp
(ꢀC)
Method A Method B
Time Yield Time Yield
(min) (%)a (min) (%)a
Phenol
b-ketoester
Coumarin
10
10
94
92
2
3
96 185[12a]
95
180[12c]
15
10
93
95
3
2
95 257[12b]
96 242[12a]
10
15
96
92
2
3
96 134[12d]
94 195[12b]
10
10
95
93
3
2
96 280[12a]
95 187[12d]
(Continued)

Ceric Ammonium Nitrate
2085
Table 1. Continued
Method A Method B
Mp
(ꢀC)
Time Yield Time Yield
(min) (%)a (min) (%)a
Phenol
b-ketoester
Coumarin
15
10
95
96
3
3
96 245[12b]
97 264[12b]
10
94
3
94 285[12b]
15
15
94
93
3
3
95 153[12b]
96 166[12b]
aYields refer to pure products, and all products were characterized by com-
parison of their physical data and 1H NMR, IR, and mass spectral data with
those of authentic samples.
EXPERIMENTAL
General Procedure: Conventional Heating Method (Method A)
A mixture of the phenol 1 (1 mmol), b-ketoester 2 (1 mmol), and CAN
(0.1 mmol) was stirred at 110 ꢀC for the appropriate time according to
(Table 1). Completion of the reaction was indicated by thin-layer chro-
matography (TLC). The reaction was cooled to room temperature,
diluted with ethyl acetate, washed with water, and dried over Na2SO4.

2086
Y. T. Reddy et al.
The solvent was removed under vacuum, and the residue was purified
by flash chromatography to yield the corresponding coumarin 3.
Microwave Irradiation Method (Method B)
A mixture of the phenol 1 (1 mmol), b-ketoester 2 (1 mmol), and CAN
(0.1 mmol) was added, and the mixture was inserted in a microwave oven
(BPL, 800T model) on a silica-gel solid support and irradiated at 300 W
for the appropriate time (Table 1). Completion of the reaction was indi-
cated by TLC. The reaction was cooled to room temperature, diluted
with ethyl acetate, washed with water, and dried over Na2SO4. The sol-
vent was removed under vacuum, and the residue was purified by flash
chromatography to yield the corresponding coumarin 3.
CONCLUSION
We have demonstrated an efficient and very simple procedure for the
synthesis of substituted coumarins by the Pechmann condensation of
phenols with b-ketoesters in solvent-free media under conventional
heating and microwave irradiation using CAN, which is an inexpensive,
nontoxic, and readily available catalyst. Prominent among the advan-
tages of this new procedure are easy workup, good yields, short reaction
times, and operational simplicity.
ACKNOWLEDGMENT
The authors are thankful to UGC, New Delhi, for financial assistance
1
and to the director, IICT, Hyderabad, for H NMR and mass spectral
analysis.
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