D. Subhas Bose et al. / Tetrahedron Letters 43 (2002) 9195–9197
9197
ing groups in the para position to the site of elec-
trophilic substitution gave maximum yields under mild
reaction conditions in a short period of time. Phenol
(entry 5) required a higher reaction temperature and
longer reaction duration, as no electron-donating group
is present. m-Methoxyphenol (entry 2) showed no
detectable demethylation under the reaction conditions.
Similarly, 1-naphthol (entry 7) requires a slightly higher
temperature and longer reaction time. When the con-
densation of m-aminophenol (entry 6) with ethyl 4,4,4-
trifluoroacetoacetate is carried out, the major product is
the coumarin 2h and 10% yield of quinoline 2i was
obtained.14 A literature survey revealed that, resace-
tophenone (entry 8) failed to react to give a coumarin
derivative in the presence of sulfuric acid as the cata-
lyst.6 However, the reaction was observed under alu-
minium chloride catalysts,8 but required a temperature
of 130°C in nitrobenzene as the solvent. In contrast, the
indium(III) chloride furnished moderate yields of the
product at 65°C.
4. (a) von Pechmann, H.; Duisberg, C. Chem. Ber. 1884, 17,
929; (b) Johnson, 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.
5. Yavari, I.; Hekmat-Shoar, R.; Zonouzi, A. Tetrahedron
Lett. 1998, 39, 2391.
6. Sethna, S.; Phadke, R. Org. React. (New York) 1953, 7,
1–58.
7. Russell, A.; Frye, J. R. Org. Synth. 1941, 21, 22.
8. Sethna, S. M.; Shah, N. M.; Shah, R. C. J. Chem. Soc.
1938, 228.
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. Woods, L. L.; Sapp, J. J. Org. Chem. 1962, 27, 3703.
11. (a) Chaudhari, D. A. Chem. Ind. 1983, 568; (b) Hoef-
nagel, A. J.; Gunnewegh, E. A.; Downing, R. S.; van
Bekkum, H. J. Chem. Soc., Chem. Commun. 1995, 225;
(c) de la Hoz, A.; Moreno, A.; Vazquez, E. Synlett 1999,
608; (d) Frere, S.; Thiery, V.; Besson, T. Tetrahedron
Lett. 2001, 42, 2791.
12. (a) Loh, T.-P.; Pei, J. J. Chem. Soc., Chem. Commun.
1996, 2315; (b) Babu, G.; Perumal, P. T. Aidrichim. Acta
2000, 33, 16; (c) Ranu, B. C. Eur. J. Org. Chem. 2000,
2347; (d) Li, J.; Li, C. J. Tetrahedron Lett. 2001, 42, 793.
13. Atkins, R.; Bliss, D. J. Org. Chem. 1978, 43, 1975.
14. Typical experimental procedure: A mixture of resorcinol
(1.1 g, 10 mmol) and ethyl acetoacetate (1.3 g, 10 mmol)
was heated under reflux (65°C) in the presence of in-
dium(III) chloride (222 mg, 10 mol%) for 1 h (TLC)
under nitrogen. The reaction mixture, after being cooled
to room temperature was poured onto crushed ice (40 g)
and stirred for 5–10 min. The crystalline products were
collected by filtration under suction (water aspirator),
washed with ice-cold water (40 ml) and then recrystallized
from hot ethanol to afford pure 7-hydroxy-4-methylcou-
marin 2a as colorless prisms (1. 73 g, 98%), mp 185–
187°C (lit.6 mp 186–187°C).
In conclusion, the present procedure of the synthesis of
coumarins by the indium(III) chloride catalyzed con-
densation of phenol and b-ketoesters provides an
efficient and much improved modification of the von
Pechmann reaction. In addition to its simplicity and
mild reaction conditions, this method has the ability to
tolerate a wide variety of substitutions in both compo-
nents. Thus, this method will offer easy access to substi-
tuted coumarins with varied substitution patterns in
high yields. We believe, our procedure will find impor-
tant applications in the synthesis of coumarins.
References
1. O’Kennedy, R.; Thornes, R. D. Coumarins: Biology,
Applications and Mode of Action; John Wiley & Sons:
Chichester, 1997.
2. Zabradnik, M. The Production and Application of Fluo-
rescent Brightening Agents; John Wiley & Sons: New
York, 1992.
3. Murray, R. D. H.; Mendez, J.; Brown, S. A. The Natural
Coumarins: Occurrence, Chemistry and Biochemistry;
John Wiley & Sons: New York, 1982.
This procedure was followed for the preparation of all
the 4-substituted coumarins listed in Table 1. All the
compounds were identified by comparison of analytical
data (IR, 1H NMR, and mass spectra) and mp with those
reported.