Selectfluor: A simple and efficient catalyst for the synthesis of substituted coumarins under solvent-free conditions

Article abstract of DOI:10.1002/jhet.5570430233

Selectfluor is used as an alternative catalyst to conventional catalysts for the synthesis of substituted coumarins via Pechmann condensation of phenols with β-ketoesters under solvent-free conditions at 120 °C. This method of synthesis is simple, cost-effective, requires short reaction time, solvent-free and gives good yields.

Full text of DOI:10.1002/jhet.5570430233

TM
Selectfluor : A Simple and Efficient Catalyst for the Synthesis of
Mar-Apr 2006
477
Substituted Coumarins Under Solvent-Free Conditions
B. Sunil Kumar, Y. Thirupathi Reddy, P. Narsimha Reddy, P. S. Kumar, B. Rajitha*
Department of Chemistry, National Institute of Technology, Warangal, India
Fax: 0091-9712-2459547; E-mail: rajitabhargavi@yahoo.com
Received April 30, 2005
TM
Selectfluor is used as an alternative catalyst to conventional catalysts for the synthesis of substituted coumarins
via Pechmann condensation of phenols with β-ketoesters under solvent-free conditions at 120 °C. This method
of synthesis is simple, cost-effective, requires short reaction time, solvent-free and gives good yields.
J. Heterocyclic Chem., 43, 477 (2006).
Introduction.
context of environmental impact, these methods are not
attractive as it requires catalyst in excess, for example sul-
phuric acid in 10-12 equivalents [15], trifluoroacetic acid
Coumarins and chromones occupy a special place in the
realm of natural and synthetic organic chemistry. This
group of compounds display a wide range of applications
[1,2] as fragrances, pharmaceuticals, additives to food and
cosmetics, agrochemicals, optical brightening agents, fluo-
rescent brighteners [3] and also posses biological activities
like antihelminthic, hypnotic, insecticidal and anticoagu-
lant [4] properties. Coumarins also act as intermediates for
the synthesis of fluorocoumarins, chromenes, coumarones
and 2-acyl resorcinols [5]. The Pechmann reaction is a
common method for the synthesis of coumarins [6] that
involves the condensation of phenols and β-ketoesters in
the presence of acidic catalysts. In addition to this reaction,
several routes have been reported for the synthesis of
coumarins including Knoevenagel [7], Reformatsky [8]
and Wittig [9] reactions. However, the Pechmann reaction
is a most commonly used and important method for the
synthesis of coumarins. Several types of acidic reagents,
in 3-4 equivalents [10b] and P O is required in 5 fold
2
5
excess [16]. Further, such reactions required long reaction
time and in some cases gave lower yields. Consequently it
is necessary to develop more effective, non-stoichiometric
alternative catalyst for the synthesis of coumarins.
However, there were no reports for the synthesis of
TM
coumarins using selectfluor
selectfluor
as a catalyst. Recently
TM
has been introduced commercially as an
electrophilic fluorinating agent. Selectfluor
TM
is a low-
cost readily available acidic material and recently it has
been employed as an efficient Lewis acid catalyst for the
one-pot allylation reactions of imines, hydrolysis of
acetals, dithia acetals and tetrahydropyranyl ethers and for
the synthesis of β-hydroxy thiocyanates [17]. Herein, we
TM
report the use of selectfluor as a new and efficient cata-
lyst for the synthesis of substituted coumarins via
Pechmann condensation of phenols and β-ketoesters under
solvent-free conditions at 120 °C.
such as sulphuric acid, hydrochloric acid, polyphosphoric
-2
acid, trifluoroacetic acid, solid superacid [ZrO /SO (or)
2
4
-2
TiO /SO ], ZnCl , POCl , P O , AlCl , FeCl have been
2
4
2
3
2
5
3
3
Results and Discussion.
used for this condensation [10]. Recently, cation exchange
resins [11] and solid acid catalysts [12] have been used for
the synthesis of coumarins. The Pechmann condensation
reaction has also been attempted using microwave irradia-
tion [13] and ionic liquids [14]. However, in the current
The Pechmann condensation of resorcinol with eth-
ylacetoacetate was selected as an example to test the
TM
feasibility of selectfluor
used as a catalyst. To
TM
optimize the molar stoichiometry of selectfluor
and
Scheme I

478
B. S. Kumar, Y. T. Reddy, P. N. Reddy, P. S. Kumar, B. Rajitha
Vol. 43

tm
Mar-Apr 2006
479
Selectfluor : A Simple and Efficient Catalyst
[2] R. D. H. Murray, J. Medez, S. A. Brown, The Natural
Coumarins: Occurrence, Chemistry and Biochemistry, Wiley: New
York (1982).
[3] M. Maeda, Laser Dyes, Academic Press: New York
(1984).
temperature, we carried out several experiments at
various temperatures under solvent-free conditions.
The best result was obtained with 0.5:1:1 molar ratio
TM
of selectfluor , resorcinol and ethylacetoacetate
respectively at 120 °C.
In conclusion, we have demonstrated a simple, cost-
effective and efficient alternative method for the prepara-
[4] L. A. Singer, N. P. Kong, J. Am. Chem. Soc., 88, 5213
(1966).
[5] S. M. Sethna, N. M. Shah, Chem. Rev., 36, 1 (1945).
[6] S. M. Sethna, R. Phadke, Org. React., 7, 1 (1953).
[7a] G. Jones, Org. React., 15, 204 (1967); [b] F. Bigi, L.
Chesini, R. Maggi, G. Sartori, J. Org. Chem., 1033 (1999).
[8] R. L. Shirner, Org. React., 1, 1 (1942).
[9a] N. S. Narasimhan, R. S. Mali, M. V. Barve, Synthesis, 906
(1979); [b] I. Yavari, R. Hekmat-Shoar, A. Zonousi, Tetrahedron
Lett., 39, 2391 (1998).
tion of substituted coumarins via Pechmann condensation
TM
using selectfluor
as catalyst. Prominent among the
advantages of this method are operational simplicity, good
yields in short reaction times, solvent-free conditions, and
easy workup procedure employed.
[10a] H. J. Appel, Chem. Soc., 1031 (1935); [b] L. L. Woods, J.
Sapp, J. Org. Chem., 27, 3703 (1962); [c] Z. S. Ahmed, R. D. Desai,
Proc. Indian. Acad. Sci., 5a, 277 (1937); Chem. Abstr., 31, 5785
(1937); [d] R. Robinson, F. J. Weygand, J. Chem. Soc., 386 (1941).
[11] E. V. O. John, S. S. Israelstam, J. Org. Chem., 26, 240
(1961).
[12a] A. J. Hoefnagel, E. A. Gennewagh, R. S. Downing, H. V.
Bekkum, J. Chem. Soc. Chem. Commun., 225 (1995); [b] R.
Pankajkumar Singh, U. Devendrapratap Singh, D. Shriniwas Samant,
Synlett, 11, 1909 (2004).
[13a] V. Singh, J. Singh, K. P. Kaur, G. L. Kad, J. Chem. Res.,
Synop. 58 (1997); [b] J. Singh, J. Kaur, S. Nayyar, G. L. Kad, J.
Chem. Res. Synop. 280 (1998); [c] A. de la Hoz, A. Moreno, E.
Vazquez, Synlett, 608 (1999); [d] S. Frere, V. Thiery, T. Besson,
Tetrahedron Lett., 42, 2791 (2001).
EXPERIMENTAL
General Procedure.
To the weighed quantity of phenol (10 mmol) and β-ketoester
TM
(10 mmol), the selectfluor
(5 mmol) was added and the reac-
tion mixture was stirred at 120 °C. After completion of the reac-
tion at the desired time as indicated in Table, the reaction mixture
was poured into cold water and the resultant product was col-
lected by filtration. The products were further purified by col-
umn chromatography. All the compounds are well known and in
agreement with spectral and physical data.
Acknowledgement.
[14] C. Amit Khandekar, M. Bhushan Khadilkar, Synlett, 1,
152 (2002).
[15] A. Russell, J. R. Frye, Org. Synth., 21, 22 (1941).
[16a] H. Simmonis, P. Remmert, Chem. Ber., 47, 2229 (1914);
[b] A. Robertson, W. F. Sandrock, C. B. Henry, J. Chem. Soc., 2426
(1931).
The authors are thankful to UGC, New Delhi for financial
assistance and to the director, IICT, Hyderabad for H NMR and
mass spectral analysis.
1
REFERENCES AND NOTES
[17a] J. Liu, C. H. Wong, Tetrahedron Lett., 43, 3915 (2002); [b]
J. Liu, C. H. Wong, Tetrahedron Lett., 43, 4037 (2002); [c] J. S.
Yadav, B. V. S. Reddy, Ch. Srinivas Reddy, Tetrahedron Lett., 45,
1291 (2004).
[1] R.O. Kennedy, R. D. Thornes, Coumarins: Biology,
Applications and Mode of Action, Wiley and Sons: Chichester
(1997).