Sulfated zirconia, a mild alternative to mineral acids in the synthesis of hydroxycoumarins

Article abstract of DOI:10.1016/j.tetlet.2006.03.030

Sulfated zirconia (1%) was employed as Pechmann's catalyst without solvent or in some cases using a small amount of ethanol to obtain coumarins in moderate to good yields. With this procedure, no significant acidic waste was obtained and an environmental friendly alternative to obtain coumarins is provided.

Full text of DOI:10.1016/j.tetlet.2006.03.030

Tetrahedron Letters 47 (2006) 3279–3281
Sulfated zirconia, a mild alternative to mineral acids in the
synthesis of hydroxycoumarins
a,b
Juan Carlos Rodrıguez-Domınguez and Gilbert Kirschb,
*
´
´
aDepartamento de Quı´mica, Centro de Quı´mica Farmace´utica, Calle 200 y 21, Atabey, Playa, CP. 11600, Ciudad de la Habana, Cuba
bLaboratoire d’Inge´nierie Mole´culaire et Biochimie Pharmacologique (LIMBP), Universite´ de Metz, 1, Boulevard Arago,
57078 Metz, France
Received 17 January 2006; revised 3 March 2006; accepted 7 March 2006
Available online 20 March 2006
Abstract—Sulfated zirconia (1%) was employed as Pechmann’s catalyst without solvent or in some cases using a small amount of
ethanol to obtain coumarins in moderate to good yields. With this procedure, no significant acidic waste was obtained and an envi-
ronmental friendly alternative to obtain coumarins is provided.
Ó 2006 Published by Elsevier Ltd.
1. Introduction
zirconia (1% w/w) neat or in alcoholic media, allows
the coumarins to be obtained in good yields (Scheme 1).
Pechmann’s1 reaction is a simple and easy procedure to
synthesize coumarins in good yields by reacting phenols
and b-ketoesters in the presence of acidic catalysts. The
classical procedure employs large amounts of sulfuric
acid as a catalyst, and therefore, produces a large
amount of strongly acidic waste that has to be treated
causing inconvenience for industry and environment.
Other catalysts such as Lewis acids,2 ionic liquids,3
and recently, zirconium tetrachloride4 have been
employed, but these methods also generate strongly
acidic waste.
In general, reactions take place with 1% sulfated zirconia
in neat (or small amount of ethanol) conditions by heat-
ing at 80 °C for 24 h giving high yields (Table 1). When
working with ethyl 2- or 4-chloroacetoacetate, the reac-
tion should be carried out at temperatures between 60
and 65 °C in order to avoid resinification of the material.
Yields are not affected by longer reaction time or
increases in the amount of catalyst. Only for obtaining
3-chloro-7-hydroxy 4-methyl coumarin and 7,8-dihy-
droxy 4-methyl coumarin (see Table 1), a greater amount
of SZr (10% w/w) has to be used. We have focused our
attention on hydroxycoumarins because they are useful
intermediates with potential biological activity.
In efforts to solve this problem resin5 and zeolite6 bared
catalysts have been used, but the yields obtained were
not satisfactory. Sulfated zirconia (SZr) is an acidic cat-
alyst, which is not as strong as inorganic acids. It has
been employed in the nitration of chlorobenzene,7 dehy-
dration of alcohols,8 synthesis of benzodiazepine deriva-
tives,9 alkane isomerizations10 and acylation of aromatic
rings.11
We have found that sulfated zirconia is a useful catalyst
for obtaining hydroxy coumarins in good yields through
an environmentally safe procedure that does not
produce acidic (or toxic) waste. The spectral data and
R1
In order to obtain coumarins in an environmental
friendly procedure and taking as reference a previous
work with zirconyl chloride octahydrate,12 we found
that substitution of strong acidic catalysts by sulfated
R2
SZr
β-Ketoester
R
R
80 ºC, 24 h
or
60-65 ºC 24 h
OH
O
O
Keywords: Coumarins; Pechmann’s reaction.
R = OH
R1 = CH3, CH2Cl
R2 = H, Cl
*
Corresponding author. Tel.: +33 387315295; fax: +33 387315801;
e-mail addresses: jcrdchem@yahoo.com; kirsch@univ-metz.fr
Scheme 1.
0040-4039/$ - see front matter Ó 2006 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2006.03.030

3280
J. C. Rodrı´guez-Domı´nguez, G. Kirsch / Tetrahedron Letters 47 (2006) 3279–3281
Table 1. Coumarins prepared and yields obtained
Phenols
Product
Yield (%), Mpobt (°C), Mplit (°C)
CH3
91, 186–189, 18814
HO
HO
OH
OH
HO
O
O
CH3
Cl
O
87,a,b,c 236–240, 236,15a 24015b
HO
O
CH2Cl
91,b,c 190–191, 18516
HO
HO
OH
OH
HO
HO
O
O
O
CH3
92,a 242–244, 241–2434
O
OH
OH
CH3
Cl
O
84,b,c 267–268, 26517
OH
HO
HO
HO
HO
O
OH
OH
CH2Cl
85,b,c 200–201, 198–19918
OH
HO
O
O
OH
OH
OH
OH
CH3
52, 289–290, 292–29319
O
OH
O
HO
OH
OH
OH
OH
CH3
Cl
O
74,b,c 317–319, 306–30817
HO
HO
OH
OH
O
HO
HO
CH2Cl
93,b,c 246–248, 243–24520
O
O
a 10% of SZr was employed.
b The reaction was carried out at 60–65 °C and 1 mL of ethanol/g of phenol was added after 2 h.
c To enable workup of the reaction, the mixture was diluted with 1 mL of ethanol/g of phenol before pouring it into water.
melting points of the synthesized coumarins match those
reported in the literature.
silica gel plates ALUGRAM Sil G/UV 254 and chloro-
form–ethyl acetate–acetic acid (8:6:1) was used as an
1
eluent. The H and 13C NMR spectra were recorded
on
a
AC Bruker 250 MHz spectrometer using
2. Experimental
DMSO-d6 as a solvent. The chemical shifts are reported
in ppm and coupling constants (J) in Hz. Melting
points were determined on a Stuart Scientific SMP 3
capillary melting point apparatus and are uncorrected.
Reagents were purchased from ACROS Organics. Thin
layer chromatography (TLC) was performed by using

J. C. Rodrı´guez-Dom´ınguez, G. Kirsch / Tetrahedron Letters 47 (2006) 3279–3281
3281
2. (a) Miyano, M.; Dorn, C. R. J. Org. Chem. 1972, 37, 259–
268; (b) Bose, D. S.; Rudradas, A. P.; Babu, M. H.
Tetrahedron Lett. 2002, 43, 9195–9197; (c) De, S. K.;
Gibbs, R. A. Synthesis 2005, 8, 1231–1233.
3. Potdar, M. K.; Mohile, S. S.; Salunkhe, M. M. Tetra-
hedron Lett. 2001, 42, 9285–9287.
Sulfated zirconia was prepared as described by Sun
et al.13
3. Typical procedure
4. Sharma, G. V. M.; Reddy, J. J.; Lakshmi, P. S.; Krishna,
P. R. Tetrahedron Lett. 2005, 46, 6119–6121.
5. John, E. V. O.; Israelstam, S. S. J. Org. Chem. 1961, 26,
240–242.
6. Gunnewegh, E. A.; Hoefnagel, A. J.; Bekkum, H. V. J.
Mol. Cat. A: Chem. 1995, 100, 87–92.
7. Yadav, G. D.; Nair, J. J. Catal. Lett. 1999, 62, 49–52.
8. Wilson, N. G.; McCreedy, T. Chem. Commun. 2000, 733–
734.
9. Reddy, B. M.; Sreekanth, P. M. Tetrahedron Lett. 2003,
44, 4447–4449.
Sulfated zirconia (1% weight of the phenol) was added
to a mixture of equimolar quantities of phenols and aceto-
acetyl esters and left at 80 °C or 60–65 °C (see ‘b’ in
Table 1) with rapid stirring for 24 h. The reaction was
monitored by TLC. When all the starting materials were
consumed and while hot the mixture was poured into
cold water (20 mL/g of starting phenol) with a rapid
stirring (see ‘c’ in Table 1). The precipitate was filtered,
washed with cold water and dried at 50 °C overnight,
yielding the hydroxycoumarins.
10. Adeeva, V.; Liu, H. Y.; Xu, B. Q.; Sachtler, W. M. H.
Topics Catal. 1998, 6, 61–76.
11. Deutsch, J.; Quaschning, V.; Kemnitz, E.; Auroux, A.;
Ehwald, H.; Lieske, H. Topics Catal. 2000, 13, 281–285.
Acknowledgements
´
´
12. Rodrıguez-Domınguez, J. C.; Kirsch, G. Synthesis, in
press.
We want to thank the Programme Alban, the European
Union Programme of High Level Scholarships for Latin
America (scholarship No. E04D040745CU) and the
13. Sun, Y.; Ma, S.; Du, Y.; Yuan, L.; Wang, S.; Yang, J.;
Deng, F.; Xiao, F. S. J. Phys. Chem. B 2005, 109, 2567–
2572.
´
Conseil Regional de Lorraine, France, for supporting
14. Reddy, B. M.; Reddy, V. R.; Giridhar, D. Synth.
Commun. 2001, 31, 3603–3608.
´
this work, Mrs. Veronique Poddig for recording the
15. (a) Pechmann, V. Chem. Ber. 1901, 34, 354–362; (b)
Grover, J. K. J. Sci. Ind. Res. 1952, 11B, 50–55.
16. Dausse Lab., DE Patent 1929839, 1969, Chem. Abstr.
1970, 72, 66823p.
´
NMR spectra and Dr. Stephanie Hesse for the helpful
discussion of the manuscript.
17. Chakravarti, D. J. Indian Chem. Soc. 1931, 8, 407–409.
18. Khaikin, M. S.; Petrova, N. L.; Kukhtin, V. A. Zh.
Obshch. Khim. 1963, 33, 3941–3943.
References and notes
1. (a) Pechmann, V. H.; Duisberg, C. Chem. Ber. 1884, 17,
929–979; (b) Kaufman, K. D.; Kelly, R. C.; Eaton, D. C.
J. Org. Chem. 1967, 32, 504–506.
19. Canter, J. J. Chem. Soc. 1931, 1255–1264.
20. Smitha, G.; Sanjeeva-Reddy, C. Synth. Commun. 2004, 34,
3997–4004.