Professional Documents
Culture Documents
Abstract—An energy-efficient protocol has been developed for solvent-free reactions that are mildly exothermic but not spontane-
ous. The exothermic reaction mixture—on several g-scale—is exposed for about 30 s to low power (about 200 W) microwaves and
then the microwave oven is switched off. After this short burst of energy, the exothermic reaction gets initiated and proceeds on its
own to completion. A number of coumarins were synthesized by the Pechmann reaction using this strategy.
Ó 2006 Elsevier Ltd. All rights reserved.
In 1883, Pechmann described an efficient synthesis of the reactants for an exothermic reaction (and a catalyst,
coumarins (3) that involved the condensation of phenols if required) to a large volume of water with efficient stir-
(1) with b-keto esters (2) (Scheme 1).1,2 ring. The exothermic reaction starts in a few minutes
and proceeds to completion. The insoluble reaction
The Pechmann reaction is versatile: a wide variety of product crystallizes out in a nearly pure form and in
substituted phenols and b-keto esters can generate cou- high yield. Thus, the condensation of salicylaldehydes
marins in good yield with substituents in the phenolic (5) and malonic esters (6) by this protocol produces cou-
nucleus and/or in the heterocyclic ring. Various con- marins (7) in high yield (Scheme 2).
densing agents have been used including metal chlorides
and phosphorus oxychloride. Solvents such as alcohol, It was observed that the Pechmann reaction for couma-
ether, and benzene have been favored. Under some con- rins (e.g., involving the interaction of resorcinol, ethyl
ditions, chromones (4) may also be formed.
CH2(CO2Et)2 B-
+
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.01.147
2424 M. S. Manhas et al. / Tetrahedron Letters 47 (2006) 2423–2425
acetoacetate, and p-toluenesulfonic acid) under the In the course of our recent studies on solvent-free reac-
water-based biphasic reaction conditions failed to pro- tion mixtures, it had been noticed that not all exothermic
duce any coumarin (Scheme 3). A different procedure reactions are spontaneous; many of them require a short
developed in our laboratory for exothermic reactions burst of energy for the initiation of the reaction. After
was then tested. such initiation, the exothermic reaction proceeds on its
own to completion—without additional energy input.
OEt
HO O O
O
HO OH
2 CO2Et 81
HO O O
HO OH O O
3 96
C2 H5 OEt
C 2 H5
HO O O
HO OH O O
4 92
C6 H5 OEt
C 6 H5
HO OH HO O O
O O
5 86
OEt
OH OH
OH
OH
O O HO O O
HO OH
6 90
OEt
OH
OH
HO O O
O O
HO OH
7 82
C6 H5 OEt
C6 H 5
HO OH HO O O
O
8 CO2Et 80
OH OH
M. S. Manhas et al. / Tetrahedron Letters 47 (2006) 2423–2425 2425
H
NH2 N
CH3CO2H
+ (CH3CO)2O
O O O MW O
O 150 W
HO HO
+ + + p-TSA 5 min
EtO NH
OEt H N NH2
Scheme 4. 2
O H
503 g 300 g 25 g N O
650 g
H
1.051 kg (92%)
was isolated in high yield. This new energy-saving proce-
dure was found to be useful for the efficient preparation Scheme 5.
of several coumarins (Table 1).
Various b-keto esters were used successfully for the records it and can duplicate it for future repeat runs.
Pechmann reaction (catalyzed by p-TSA) with resor- Since only a very short burst of low level microwave
cinol, pyrogallol and other phenols. A wide variety of energy is needed, it is quite sufficient and convenient to
coumarins were obtained by this method in about use an inexpensive domestic microwave oven for the pres-
20 min, under solvent-free, green reaction conditions. ent work.