J . Org. Chem. 1999, 64, 1033-1035
1033
In recent years many efforts have been made to
prepare olefinic compounds via Knoevenagel condensa-
tion under heterogeneous catalysis: in particular
aluminum oxide,9 Xonotlite/tert-butoxide,10 cation-ex-
changed zeolites,11 alkali-containing MCM-41,12 and
bentonitic clay13 were employed.
Mon tm or illon ite KSF a s a n In or ga n ic,
Wa ter Sta ble, a n d Reu sa ble Ca ta lyst for
th e Kn oeven a gel Syn th esis of
Cou m a r in -3-ca r boxylic Acid s
Franca Bigi,* Luca Chesini, Raimondo Maggi, and
Giovanni Sartori
As part of our research program concerning the use of
solid acids in fine chemicals preparation,14 we have
investigated the Knoevenagel synthesis of coumarin
derivatives under montmorillonitic clay catalysis.
Dipartimento di Chimica Organica e Industriale
dell’Universita`, Viale delle Scienze, I-43100 Parma, Italy
Received September 3, 1998
Resu lts a n d Discu ssion
In tr od u ction
To study this process, we have examined the model
reaction of salicylaldehyde (1a ) (10 mmol) with diethyl
malonate (2x) (15 mmol) in the presence of 1 g of catalyst.
We observed that montmorillonite KSF15a and K1015b
promoted the process affording the expected heterocyclic
product 3, KSF being the more efficient promoter of the
reaction (Table 1).
The increasing demands of environmental legislation
have been prompting the chemical industry to minimize
or, preferably, eliminate waste production in chemical
manufacture. Environmentally benign processes are
requested for primary prevention of pollution, and enviro-
economic factors will become the driving force behind new
products and processes.1
The use of heterogeneous catalysts, in particular
zeolites and clays, has reached great development in
different areas of organic synthesis due to their environ-
mental compatibility combined with the good yields and
selectivities that can be achieved.2
These results suggest that the clay behaves as a ditopic
catalyst containing both acid and basic sites. The basic
sites, ascribable to the negative charges dispersed over
entire sheets of oxygen atoms,16 activate the Knoevenagel
condensation. Further, the acid sites, which are mainly
due to the polarized interlayer water molecules, promote
the R-pyrone ring formation by intramolecular transes-
terification.17
Coumarin (2H-1-benzopyran-2-one) and coumarin
derivatives are natural compounds3 and are important
chemicals in the perfume, cosmetic, and pharmaceutical
industrial production.4
To reduce the employment of ecologically suspected
solvents, we have chosen to carry out the reactions in
the absence of solvent or in water. Indeed water is
The Knoevenagel reaction,5 a century old reaction, is
one of the most common synthetic methods to produce
coumarins. The process consists of the condensation of
salicylic aldehydes with malonic acid or esters giving the
coumarin-3-carboxylic acids or esters that successively
undergo decarboxylation. The reaction is catalyzed by
weak bases5 or by suitable combinations of amines and
carboxylic6 or Lewis7 acids under homogeneous condi-
tions. A solid-phase synthesis has just been published.8
(9) (a) Texier-Boullet, F.; Foucaud, A. Tetrahedron Lett. 1982, 23,
4927. (b) Cabello, J . A.; Campelo, J . M.; Garcia, E.; Luna, D.; Marinas,
J . M. J . Org. Chem. 1984, 49, 5195.
(10) (a) Chalais, S.; Laszlo, P.; Mathy, A. Tetrahedron Lett. 1985,
26, 4453. (b) Laszlo, P. Acc. Chem. Res. 1986, 19, 121.
(11) (a) Corma, A.; Mart`ın-Arande, R. M. J . Catal. 1991, 130, 130.
(b) Reddy, T. I.; Varma, R. S. Tetrahedron Lett. 1997, 38, 1721.
(12) Kloetstra, K. R.; van Bekkum, H. J . Chem. Soc., Chem.
Commun. 1995, 1005.
(13) Delgado, F.; Tamariz, J .; Zepeda, G.; Landa, M.; Miranda, R.;
Garc`ıa, J . Synth. Commun. 1995, 25, 753.
(1) (a) Cusumano, J . A. Chemtech 1992, 482. (b) Clark, J . A.;
Macquarrie, D. J . Chem. Soc. Rev. 1996, 303. (c) Sheldon, R. A. Chem.
Ind. 1997, 12.
(2) (a) Balogh, M.; Laszlo, P. Organic Chemistry using Clays,
Springer-Verlag: New York, 1993. (b) Thomas, J . M. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 913. (c) Barthomeuf, D. Catal. Rev. 1996, 38,
521. (d) Holderich, W. F. In Comprehensive Supramolecular Chemistry;
Atwood, J . L., Davies, J . E. P., MacNicol, D. D., Vo¨gtle, F., Eds.;
Pergamon Press: Oxford, 1996; Vol. 7, pp 671-692.
(3) (a) Dean, F. M. Naturally Occurring Oxygen Ring Compouds;
Butterworth: London, 1963. (b) Soine, T. O. J . Pharm. Sci. 1964, 53,
231. (c) Murray, R. D. H.; Mendez, J .; Brown, S. A. The Natural
Coumarins: Occurrence, Chemistry and Biochemistry; Wiley: New
York, 1982.
(4) (a) Meuly, W. C. Kirk-Othmer Encyclopedia of Chemical Technol-
ogy, 3rd ed.; J ohn Wiley and Sons: New York, 1979; Vol. 7, pp 196-
906. (b) Stuart, D. M.; Hruschka, J . K. Ibid. Vol. 16, pp 951-955. (c)
Taylor, W. I.; Chant, B.; van Loveren, G. Ibid. Vol. 4, p 15.
(5) (a) Knoevenagel, E. Chem. Ber. 1896, 29, 172; 1898, 31, 730. (b)
J ones, G. Organic Reactions; Wiley: New York, 1967; Vol. 15, p 204.
(c) Tietze, L. F.; Beifuss, U. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press: Oxford,
1991; Vol. 2, Chapter 1.11, pp 341-394.
(6) Baltorowicz, M. Pr. Inst. Przem. Org. 1970, 2, 33: Chem. Abstr.
1973, 78, 58190p.
(7) Green, B.; Crane, R. I.; Khaidem, I. S.; Leighton, R. S.; Newaz,
S. S.; Smyser, T. E. J . Org. Chem. 1985, 50, 640.
(14) (a) Arienti, A.; Bigi, F.; Maggi, R.; Marzi, E.; Moggi, P.; Rastelli,
M.; Sartori, G.; Tarantola, F. Tetrahedron 1997, 53, 3795. (b) Arienti,
A.; Bigi, F.; Maggi, R.; Moggi, P.; Rastelli, M.; Sartori, G.; Trere`, A. J .
Chem. Soc., Perkin Trans. 1 1997, 1391. (c) Ballini, R.; Bigi, F.; Carloni,
S.; Maggi, R.; Sartori, G. Tetrahedron Lett. 1997, 38, 4169. (d) Bigi,
F.; Carloni, S.; Maggi, R.; Muchetti, C.; Sartori, G. J . Org. Chem. 1997,
62, 7024. (e) Bigi, F.; Carloni, S.; Maggi, R.; Muchetti, C.; Rastelli, M.;
Sartori, G. Synthesis 1998, 301. (f) Bigi, F.; Maggi, R.; Sartori, G.;
Zambonin, E. J . Chem. Soc., Chem. Commun. 1998, 513.
(15) (a) KSF is a commercial (Fluka) montmorillonite with surface
area 15 ( 10 m2/g, acidity 0.85 mequiv H+/g [determined in our
laboratory by temperature-programmed desorption of ammonia gas
(NH3-TPD)], and with the following chemical composition (average
value): SiO2 (54.0%), Al2O3 (17.0%), Fe2O3 (5.2%), CaO (1.5%), MgO
(2.5%), Na2O (0.4%), K2O (1.5%). (b) K10 is a commercial (Fluka)
montmorillonite with surface area 200 ( 10 m2/g, acidity 0.70 mequiv
H+/g [determined in our laboratory by temperature-programmed
desorption of ammonia gas (NH3-TPD)], and with the following
chemical composition (average value): SiO2 (73.0%), Al2O3 (14.0%),
Fe2O3 (2.7%), CaO (0.2%), MgO (1.1%), Na2O (0.6%), K2O (1.9%)
(16) Alberti, G.; Costantino, V. In Comprehensive Supramolecular
Chemistry; Atwood, J . L., Davies, J . E. P., MacNicol, D. D., Vo¨gtle, F.,
Eds.; Pergamon Press: Oxford, 1996; Vol. 7, pp 1-23.
(17) For montmorillonite-promoted transesterification: (a) Mitsui
Petrochemical Industries, Ltd. J pn. Kokai Tokkio Koho 59,204,153,
1984; Chem. Abstr. 1985, 102, 112894a. (b) Ponde, E. D.; Deshpande,
V. H.; Bulbule, V. J .; Sudalai, A.; Gajare, A. S. J . Org. Chem. 1998,
63, 1058.
(8) Watson, B. T.; Christiansen, G. E. Tetrahedron Lett. 1998, 39,
6087.
10.1021/jo981794r CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/08/1999