New approach to the synthesis of 3-arylcoumarins. Reaction of 3-acyl- and 3-ethoxycarbonyl-coumarins with hydrazide of p-nitrophenylacetic acid [1]

Full text of DOI:10.1023/A:1015359830129

Chemistry of Heterocyclic Compounds, Vol. 38, No. 2, 2002
LETTERS TO THE EDITOR
NEW APPROACH TO THE SYNTHESIS
OF 3-ARYLCOUMARINS. REACTION OF
3-ACYL- AND 3-ETHOXYCARBONYL-
COUMARINS WITH HYDRAZIDE
OF p-NITROPHENYLACETIC ACID
1
1
2
2
1
M. P. Nemeryuk , V. D. Dimitrova , A. L. Sedov , O. S. Anisimova , and V. F. Traven'
Keywords:
-(p-nitrophenyl)coumarins, opening and recyclization of the lactone ring in coumarins, Michael
reaction.
3-acyl(ethoxycarbonyl)coumarins,
hydrazide
of
p-nitrophenylacetic
acid,
3
3
-Arylcoumarins are usually obtained by the cyclization of mono- or ortho-substituted benzenes such as
phenols or salicylaldehydes with compounds containing phenyl substituent along with active methylene group
1, 2]. The use of coumarins themselves as starting compounds for the preparation of 3-arylcoumarins is much
[
rarer. The reaction of coumarins with phenyldiazonium salts to give 3-arylcoumarins has been reported [3].
We have found that the synthesis of 3-arylcoumarins containing electron-withdrawing substituents in
the aryl ring may be accomplished by the reaction of 3-acylcoumarins or 3-ethoxycarbonylcoumarin with
derivatives of phenylacetic acid hydrazides under Michael reaction conditions. For example, the reaction of
3
-acetyl-, 3-benzoyl- and 3-ethoxycarbonylcoumarins 1a-d with hydrazide of p-nitrophenylacetic acid (2) gave
the corresponding 3-(p-nitrophenyl)coumarins 3a and 3b.
NO2
X
O
NO2
O
+
ethanol
O
O
O
H NHN
2
HN
R
R
1
a–d
2
3a,b
1
a X = COPh, R = OMe, b X = COMe, R = H, c X = COPh, R = H, d X = COOEt, R = H;
a R = OMe, b R = H
3
_
___________________________________________________________________________________________
1
D. I. Mendeleev Russian Chemical Engineering University, 125047 Moscow, Russia; e-mail:
2
traven@main-gw.muctr.edu.ru. Pharmaceutical Chemistry Institute (TsKhLS–VNIKhFI), 119815 Moscow,
Russia; e-mail: sedov@drug.org.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2,
pp. 272-273, February, 2002. Original article submitted June 21, 2001.
0009-3122/02/3802-0249$27.00©2002 Plenum Publishing Corporation
249

The conversion of coumarins 1a-d into 3-(p-nitrophenyl)coumarins 3a and 3b was carried out in ethanol
at 18-20°C in the presence of catalytic amounts of piperidine. Thus, one drop of piperidine was added to
mixture of 3-benzoyl-8-methoxycoumarin (1a) (0.07 g, 0.25 mmol) and hydrazide 2 (0.05 g, 0.25 mmol) in
ethanol (15 ml) and stirred for 24 h at room temperature. The precipitate formed was filtered off and washed
with ethanol (5 ml) to give pale yellow crystalline 3-(p-nitrophenyl)coumarin 3a (0.05 g, 67%); mp 295-296°C
1
(
DMF). H NMR spectrum (DMSO-d
6
), δ, ppm: 3.95 (3H, s, OCH ); 7.36 (3H, s, arom); 8.02 (2H, d, arom);
3
-1
8
.34 (2H, d, arom); 8.43 (1H, s, 4-CH). IR spectrum, ν, cm : 1702, 1610, 1575, 1568. Found, %: C 64.72;
+
H 3.84; N 5.01; M 297. C16
H
11NO . Calculated, %: C 64.64; H 3.70; N. 4.71; M 297.
5
Under analogous conditions, coumarins 1b-d were converted to 3-(p-nitrophenyl)coumarin 3b by
reaction with hydrazide 2. The reaction of 1b gave 3b in 20% yield. The reaction of 1c gave 3b in 71% yield.
The reaction of 1d gave 3b in 60% yield. Coumarin 3b was obtained as fine light yellow crystals;
+
1
mp 259-261°C (DMF) (262°C [2]), M 267. C15
H
9
NO
4
. Calculated: M 267. H NMR spectrum (DMSO-d
6
),
-1
δ, ppm: 7.38-7.84 (4H, m, arom); 8.02 (2H, d, arom); 8.34 (2H, d, arom). IR spectrum, ν, cm : 1709, 1688,
1
606, 1596.
The preparation of 3-(p-nitrophenyl)coumarins 3a and 3b is a typical one-pot procedure involving
several steps and carried out analogously to the conversion of 3-acylcoumarins into 3-cyanocoumarins described
in our previous works [4, 5]. Evidence for this hypothesis was found in the detection of peaks characteristic of
-phenyl-5-pyrazolone (160 [M] , 131 [M - HCO] , 118 [M - CH CO] , 103 [PhCN] ) in the mass spectrum
+
·
+·
+·
+·
3
2
from the reaction mixture of 1c and 2. 3-Phenyl-5-pyrazolone is formed during this conversion by the reaction
of hydrazine and ethyl benzoylacetate, which is lost during the recyclization of the coumarin ring.
This method for the synthesis of 3-(p-nitrophenyl)coumarins may be considered as an alternative
supplementing the known methods for the preparation of such compounds.
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.
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250