Coumarin syntheses via Pechmann condensation in Lewis acidic chloroaluminate ionic liquid

Article abstract of DOI:10.1016/S0040-4039(01)02041-X

1-Butyl-3-methylimidazolium chloroaluminate, [bmim]Cl·2AlCl₃ ionic liquid is used as an alternative to conventional acid catalysts in the Pechmann condensation of phenols with ethyl acetoacetate leading to the formation of coumarin derivatives. The reaction time is reduced drastically even at ambient conditions. The ionic liquid plays the dual role of solvent and Lewis acid catalyst providing a quick and efficient route to the syntheses of coumarins.

Full text of DOI:10.1016/S0040-4039(01)02041-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 9285–9287
Coumarin syntheses via Pechmann condensation in Lewis acidic
chloroaluminate ionic liquid
Mahesh K. Potdar, Swapnil S. Mohile and Manikrao M. Salunkhe*
Department of Chemistry, The Institute of Science, 15 Madam Cama Road, Mumbai 400 032, India
Received 11 September 2001; revised 25 October 2001; accepted 30 October 2001
Abstract—1-Butyl-3-methylimidazolium chloroaluminate, [bmim]Cl·2AlCl3 ionic liquid is used as an alternative to conventional
acid catalysts in the Pechmann condensation of phenols with ethyl acetoacetate leading to the formation of coumarin derivatives.
The reaction time is reduced drastically even at ambient conditions. The ionic liquid plays the dual role of solvent and Lewis acid
catalyst providing a quick and efficient route to the syntheses of coumarins. © 2001 Elsevier Science Ltd. All rights reserved.
Coumarins occupy an important place in the realm of
natural and synthetic organic chemistry. They are used
as anticoagulants,1 additives in food and cosmetics2 and
in the preparation of insecticides, optical brighteners3
and dispersed fluorescent and laser dyes.4 Coumarins
have been synthesised by several methods, including
Pechmann,5a Perkin,5b Knoevenagel,5c,d Reformatsky5e
and Wittig6 reactions.
catalysts12 and by combination of solid acid catalysts
and microwave irradiation13 as an alternative to con-
ventional methods. Ionic liquids have recently gained
recognition as possible environmentally benign alterna-
tive solvents in various chemical processes. They have
attracted the attention of chemists owing to their
unique physical and chemical properties.14 Because of
their vanishingly low vapour pressure, ionic species do
not contribute to volatile organic compound emission.
They have also been referred as ‘designer solvents’,15 as
their properties can be altered by the fine-tuning of
parameters such as the choice of organic cation, inor-
ganic anion and alkyl chain attached to the organic
cation. These structural variations offer flexibility to the
chemist to devise the most idealised solvent, catering
for the needs of any particular process. Several reac-
tions have been carried out in ionic liquids, such as
Diels–Alder16a,b and Wittig reaction,16c benzoin
condensations16d and hydrogenation16e reactions and
even enzyme catalysed reactions.16f,g
The Pechmann reaction is the most widely applied
method for synthesising coumarins as it involves the
condensation of phenols with b-ketonic esters in the
presence of a variety of acidic condensing agents and
gives good yields of 4-substituted coumarins.7,8 Several
acid catalysts have been used in the Pechmann reaction
including sulfuric acid,5a phosphorus pentoxide,9 alu-
minium chloride,10 trifluoroacetic acid11 and many
more.7 However, these catalysts have to be used in
excess; for example, sulfuric acid in 10–12 equiv.,8
trifluoroacetic acid in three to 4 equiv.,11 and phospho-
rous pentoxide is required in a five-fold excess. Further,
the disposal of acid waste leads to environmental
pollution.
Chloroaluminate ionic liquids have been used in
Friedel–Crafts17 and other reactions in which they play
the dual role of Lewis acid catalyst and solvent. In
continuation of our efforts to explore new reactions in
these liquids, we have carried out the Fries rearrange-
ment in an ionic liquid.18
With the rapid development in the field of synthetic
organic chemistry, researchers from both academia and
industry have started giving serious thought to the
detrimental effect of non-green processes and chemicals
on the environment. They have successfully developed
several environmentally benign procedures to avoid, or
at least minimise, these effects. Syntheses of coumarins
have been carried out successfully using solid acid
Scheme 1. Pechmann condensation in acidic chloroaluminate
* Corresponding author. Tel./fax: (91-22) 2816750; e-mail:
ionic melt.
mmsalunkhe@hotmail.com
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02041-X

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M. K. Potdar et al. / Tetrahedron Letters 42 (2001) 9285–9287
Table 1. Syntheses of coumarins via Pechmann condensations of phenols with ethyl acetoacetate in [bmim]Cl·2AlCl3
The versatility of chloroaluminate ionic liquids encour-
aged us to carry out the Pechmann condensation in this
novel reaction medium. We report herein for the first
time, the syntheses of coumarins via Pechmann conden-
sations of phenols with ethyl acetoacetate in the Lewis
acidic [bmim]Cl·2AlCl3 ionic liquid (Scheme 1).
they are classified as basic, neutral or acidic liquids
where N is 0–0.5, 0.5 and 0.5–0.67, respectively. The
Pechmann condensation of phenols with ethyl aceto-
acetate was carried out in N=0.33, 0.5 and 0.67
liquids. Positive results were obtained only in the case
of an acidic ionic liquid as expected. The liquid
corresponding to N=0.67 gave a maximum yield in
minimum time and hence was utilised for all the reac-
tions.19
The composition of ionic liquids is expressed as
the apparent AlCl3 mole fraction, N. Accordingly,

M. K. Potdar et al. / Tetrahedron Letters 42 (2001) 9285–9287
9287
To study substituent effects on the reactivity of the
phenol, the reactions were performed on a variety of
phenols. The reactions worked well and the results are
illustrated in Table 1. For most of the substrates, the
reaction time is reduced drastically even at ambient
conditions in contrast to reported procedures,7,8 with
an excellent yield of coumarins. Substrates (entries 1–6)
having electron-donating groups in para to the site of
electrophilic substitution gave maximum yields at room
temperature in the minimum time. 3-Methoxyphenol
(entry 2) showed no detectable demethylation under the
given conditions. However, control experiments20 by
conventional method using AlCl3 in nitrobenzene
showed significant demethylation at high temperature
which is necessary to drive the reaction to completion.
1-Naphthol (entry 7) requires a slightly higher tempera-
ture and longer reaction time, due to the presence of
another phenyl ring. Similarly, phenol (entry 8)
required a higher reaction temperature and longer reac-
tion duration, as no electron-donating group is present.
A literature survey revealed that, resacetophenone
(entry 9) failed to react to give a coumarin derivative in
the presence of sulfuric acid as the catalyst. However,
the reaction was observed under aluminium chloride
catalysis,10 but required a temperature of 130°C in
nitrobenzene as the solvent. In contrast, the ionic liquid
furnished comparable yields of the product at 60°C.
Furthermore, the method succeeds in exploiting this
novel system as a Lewis acid catalyst and solvent which
is needed in the reactions in only stoichiometric
amounts.
6. (a) Narasimahan, N. S.; Mali, R. S.; Barve, M. V.
Synthesis 1979, 906; (b) Yavari, I.; Hekmat-Shoar, R.;
Zonouzi, A. Tetrahedron Lett. 1998, 39, 2391.
7. Sethna, S.; Phadke, R. Org. React. 1953, 7, 1.
8. Russell, A.; Frye, J. R. Org. Synth. 1941, 21, 22.
9. (a) Simmonis, H.; Remmert, P. Chem. Ber. 1914, 47,
2229; (b) Robertson, A.; Sandrock, W. F.; Henry, C. B.
J. Chem. Soc. 1931, 2426.
10. Sethna, S. M.; Shah, N. M.; Shah, R. C. J. Chem. Soc.
1938, 228.
11. Woods, L. L.; Sapp, J. J. Org. Chem. 1962, 27, 3703.
12. (a) John, E. V. O.; Israelstam, S. S. J. Org. Chem. 1961,
26, 240; (b) Chaudhari, D. A. Chem. Ind. 1983, 568; (c)
Hoefnagel, A. J.; Gunnewegh, E. A.; Downing, R. S.; van
Bekkum, H. J. Chem. Soc., Chem. Commun. 1995, 225.
13. (a) de la Hoz, A.; Moreno, A.; Va´zquez, E. Synlett 1999,
608; (b) Fre´re, S.; Thie´ry, V.; Besson, T. Tetrahedron
Lett. 2001, 42, 2791.
14. (a) Review: Welton, T. Chem. Rev. 1999, 99, 2071; (b)
Review: Wassercheid, P.; Keim, W. Angew. Chem., Int.
Ed. Engl. 2000, 39, 3772.
15. Freemantle, M. Chem. Eng. News 1998, 76, 32.
16. (a) Fisher, T.; Sethi, A.; Welton, T.; Woolf, J. Tetra-
hedron Lett. 1999, 40, 793; (b) Lee, C. W. Tetrahedron
Lett. 1999, 40, 2461; (c) Boulaire, V. L.; Gre´e, R. Chem.
Commun. 2000, 2195; (d) Davis, Jr., J. H.; Forrester, K.
J. Tetrahedron Lett. 1999, 40, 1628; (e) Dyson, P. J.; Ellis,
D. J.; Parker, D. G.; Welton, T. Chem. Commun. 1999, 1,
25; (f) Erbeldinger, M.; Mesiano, A. J.; Russell, A. J.
Biotechnol. Prog. 2000, 16, 227; (g) Lau, R. M.;
Rantwijk, F.v.; Seddon, K. R.; Sheldon, R. A. Org. Lett.
2000, 2, 4189.
17. (a) Boon, J. A.; Levisky, J. A.; Pflug, J. L.; Wilkes, J. S.
J. Org. Chem. 1986, 51, 480; (b) Adams, C. J.; Earle, M.
J.; Roberts, G.; Seddon, K. R. J. Chem. Soc., Chem.
Commun. 1998, 2097.
18. Harjani, J. R.; Nara, S. J.; Salunkhe, M. M. Tetrahedron
Lett. 2001, 42, 1979.
To conclude, we have successfully achieved the synthe-
ses of coumarins using phenols and ethyl acetoacetate
via Pechmann condensations in acidic chloroaluminate
ionic liquid. Further investigations on the syntheses of
coumarins via Knoevenagel condensations of o-
hydroxy arylaldehydes and the active methylene com-
pounds in these liquids are currently in progress.
19. Typical experimental procedure: To the weighed quantity
of phenol (10 mmol) and ethyl acetoacetate (11 mmol),
the ionic liquid [bmim]Cl·2AlCl3 (11 mmol) was added
and the reaction mixture was stirred at the desired time
and temperature. All additions were carried out in an
inert atmosphere. The reaction was quenched by adding 6
M HCl in cold conditions. The resultant product was
filtered. The products were further purified by column
chromatography and characterised by IR, NMR and
physical constants.
20. The reaction was carried out using 3-methoxyphenol (10
mmol), ethyl acetoacetate (11 mmol) and AlCl3 (20
mmol). A poor yield (15%) of the coumarin derivative
was obtained at room temperature for 20 min along with
2% of the demethylated product. In another experiment,
the reaction was carried out at 125°C for 1 h by using
exactly the same quantities as mentioned above. In this
case, the overall yield of coumarin derivative was 65%, of
which 32% was demethylated product.
References
1. Singer, L. A.; Kong, N. P. J. Am. Chem. Soc. 1966, 88,
5213.
2. O’Kennedy, R.; Thornes, R. D. Coumarins: Biology,
Applications and Mode of Action; Wiley
& Sons:
Chichester, 1997.
3. Zahradnik, M. The Production and Application of Fluo-
rescent Brightening Agents; Wiley & Sons, 1992.
4. Murray, R. D. H.; Mendez, J.; Brown, S. A. The Natural
Coumarins: Occurrence, Chemistry and Biochemistry;
Wiley & Sons: New York, 1982.
5. (a) v. Pechmann, H.; Duisberg, C. Chem. Ber. 1884, 17,
929; (b) Jonson, J. R. Org. React. 1942, 1, 210; (c) Jones,
G. Org. React. 1967, 15, 204; (d) Brufola, G.; Fringuelli,
F.; Piermatti, O.; Pizzo, F. Heterocycles 1996, 43, 1257;
(e) Shriner, R. L. Org. React. 1942, 1, 1.