Mendeleev Commun., 2006, 16(4), 241–242
References
Table 1 Synthesis of coumarins via von Pechmann condensation of phenol
with β-ketoesters catalysed by chlorosulfonic acid.
1
R. O. Kennedy and R. D. Thornes, Coumarins: Biology, Applications
and Mode of Action, Wiley, Chichester, 1997.
H. Dev. Peter, Oncol., 1984, 22, 259.
H. von Pechmann and C. Duisberg, Chem. Tech. Ber., 1884, 17, 929.
J. R. Jonson, Org. React., 1942, 1, 210.
G. Jones, Org. React., 1967, 15, 204.
G. Brufola, F. Fringuelli, O. Piermatti and F. Pizzo, Heterocycles, 1996,
43, 1257.
Tempera-
ture/°C
Exp. (Lit.)
2
3
4
5
6
Time/min
Exp. (Lit.)
Yield
(%)
Substrate
Product
HO
O
O
O
HO
OH
OH
10 (60)20
10 (60)20
10 (75)20
10 (75)20
98
94
7
8
R. L. Shriner, Org. React., 1942, 1, 1.
N. S. Narasimahan, R. S. Mali and M. V. Barve, Synthesis, 1979, 906.
MeO
MeO
O
10 S. Sethna and R. Phadke, Org. React., 1953, 7, 1.
11 A. Russel and J. R. Frye, Org. Synth., 1941, 21, 22.
12 H. Simmonis and P. Remmert, Chem. Ber., 1914, 21, 22.
13 A. Robertson, W. F. Sandrock and C. B. Henry, J. Chem. Soc., 1931,
2426.
14 S. M. Sethna, N. M. Shah and R. C. Shah, J. Chem. Soc., 1938, 228.
15 L. L. Woods and J. Sapp, J. Org. Chem., 1962, 27, 3703.
16 A. de la Hoz, A. Moreno and E. Va’zquez, Synlett., 1999, 608.
19 R. J. Cremylan, Chlorosulfonic Acid – a Versatile Reagent, Royal
Society of Chemistry, Cambridge, 2002.
20 S. K. De and R. A. Gibbs, Synthesis, 2005, 1231.
22 A. C. Khandekar and B. M. Khadilkar, Synlett., 2002, 152.
HO
HO
OH
OH
HO
HO
O
O
O
O
10 (30)21
10 (80)21
90
10 (60)20
10 (40)22
10 (75)20
10 (80)22
95
89
OH
OH
OH
OH
O
O
O
O
OH
OH
OH
OH
HO
HO
10 (20)20
10 (80)20
91
OH
O
O
O
O
25 (120)20 10 (110)20 88
OH
22 (20)20
20 (35)21
10 (80)20
10 (80)21
78
75
O2N
O2N
NO2
NO2
O
O
O
O
OH
OH
15 (40)20
10 (80)20
50
MeO
MeO
Received: 21st October 2005; Com. 05/2597
OH
OH
†
Typical experimental procedure. A mixture of resorcinol (1.1 g, 10 mmol)
We report the Pechmann condensation using chlorosulfonic
acid as a catalyst under solvent-free conditions (Scheme 1).† In
the presence of chlorosulfonic acid, the reaction of ethyl aceto-
acetate and resorcinol was carried out under solvent-free con-
ditions at 10 °C and resulted in the formation of 7-hydroxy-
4-methylcoumarin in 98% yield. We investigated the reactions
of a series of monohydric and polyhydric phenols with β-keto-
esters to obtain the corresponding coumarins (Table 1). In general,
we observed that the reaction proceeded faster than conven-
tional ones and the yields were comparable.
and ethyl acetoacetate (1.3 g, 10 mmol) was cooled in an ice bath.
Chlorosulfonic acid (0.2 ml) was added dropwise with constant stirring
at appropriate time (Table 1). The reaction mixture, after being cooled to
room temperature, was poured into 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 and then recrys-
tallised from methanol to afford pure 7-hydroxy-4-methylcoumarin as
1
yellowish prisms (1.74 g, 98%), mp 184–186 °C. H NMR (CDCl3) d:
2.2 (s, 3H, Me), 6.1 (s, 1H), 6.83 (d, 1H, J 2.4 Hz), 6.97 (dd, 1H, J 8.7
and 2.4 Hz), 7.5 (d, 1H, J 8.7 Hz). IR (KBr, n/cm–1): 2985, 1740, 1625.
ES/MS, m/z: 175 (M – H).
This procedure was followed for the preparation of all of the substituted
coumarins listed in Table 1. All compounds were identified by comparison
of analytical data (IR, 1H NMR and mass spectra) and melting ponts with
published data.
A grant-in-aid from UGC, New Delhi (Major Research Project)
to D. B. Shinde and a junior research fellowship to S. A. Kotharkar
are gratefully acknowledged.
242 Mendeleev Commun. 2006