One-Pot Synthesis of 3-Carboxycoumarins via Consecutive Knoevenagel and Pinner Reactions in Water

Article abstract of DOI:10.1055/s-2003-41061

Chloro-, hydroxy-, methoxy-, and tert-butyl-substituted 3-carboxycoumarins have been prepared by one-pot procedure by reaction of suitably substituted salicylaldehydes with malononitrile in water. The over-all yields are high and the protocol does not require organic solvents.

Full text of DOI:10.1055/s-2003-41061

PAPER
2331
One-Pot Synthesis of 3-Carboxycoumarins via Consecutive Knoevenagel and
Pinner Reactions in Water
O
F
ne-Pot Synth
r
esis of
3
a
-Carboxyco
n
umarins cesco Fringuelli, Oriana Piermatti,* Ferdinando Pizzo*
Dipartimento di Chimica, Università di Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
E-mail: pizzo@unipg.it
Received 20 May 2003; revised 10 July 2003
carboxycoumarins in water that is also operative when
highly hydrophobic groups such as tert-butyl groups are
present in the aromatic moiety.
Abstract: Chloro-, hydroxy-, methoxy-, and tert-butyl-substituted
-carboxycoumarins have been prepared by one-pot procedure by
reaction of suitably substituted salicylaldehydes with malononitrile
in water. The over-all yields are high and the protocol does not re-
quire organic solvents.
3
Salicylaldehydes 1 reacted with malononitrile (2) at room
temperature in aqueous basic heterogeneous medium (pH
Key words: aldol reactions, cyclizations, hydrolyses, 3-carboxy- 8.3–13.3) to give the cyanoimino ethers 4 via Knoevena-
coumarins, water
gel (1 + 2 3) and Pinner (3 4) reactions (Scheme 1).
Acid hydrolysis in situ of 4 at 90 °C produced the 3-cy-
anocoumarins 5 in high yields. These compounds could
Coumarins are an important class of natural and synthetic then be isolated by simple filtration or, without interrup-
1
compounds which display a wide variety of properties.
tion, hydrolyzed at 90 °C under basic conditions. Final
2
a–e
They are active as drugs,
found in perfumes and cos- acidification of the reaction mixture allowed the isolation
2
f
2g
2h
metics, and used in laser dyes, insecticides, photo- of 3-carboxycoumarins 6 by filtration in excellent over-all
2
i–k
graphic sensitizers and solar collectors,
and are yields without using an organic solvent.
employed as fluorescent markers in biochemistry.2
Coumarins are also exploited as intermediates and build-
l,m
CHO
CN
CN
2
n,o
CN
CN
2
OH
ing blocks in organic synthesis.
+
R
R
R
R
r.t.; t1
OH
OH
Recently, there has been great interest in 3-carboxy-
coumarins that have been used to synthesize modified
cephalosporins, penicillins, oxygen-bridged tetrahydro-
pyridones, isoureas, esters and amides which exhibit
specific inhibitors of -chymotripsin and human leuko-
cyte elastase, and polymeric compounds. Consequent-
ly, syntheses specifically aimed at 3-carboxycoumarins
have appeared in the literature. Most of them are based on
a Knoevenagel reaction between a suitably substituted
salicylaldehyde and Meldrum’s acid carried out under
1
3
4
3
4
5
6
CN
CN
NH
H
2
d,e
7
9
0 °C; t2
O
O
O
5
1
. OH ;90 °C; t3
. H
2
8
various reaction conditions. Alternative procedures in-
clude a solid-phase synthesis between diethyl malonate
bound to the Wang resin and the condensation of salicy-
COOH
R
9
O
O
laldehydes with malonic acid in the presence of clay
6
1
0
KFS. These procedures are easy, and, in some cases, en-
8
c–f,11
a: R = H; b: R = 6-Cl; c: R = 6-OH; d: R = 7-OH; e: R = 7-OMe;
f : R = 8-OH; g: R = 8-t-Bu; h: R = 5,7-(OMe)2; i : R = 6.8-(t-Bu)2
vironmentally friendly.
The 3-carboxycoumarins are
usually prepared in water, in good yields, but, when high-
ly hydrophobic substituents, such as one or two tert-butyl Scheme 1
groups are present in the aromatic ring of the molecule,
8
f
the reaction does not work in aqueous medium.
The results are illustrated in Table 1. If the process is
Continuing our work in organic synthesis performed in stopped after the Knoevenagel and Pinner reactions, the
1
2
water, we decided to investigate the use of coumarins as iminoethers 4 can be isolated by filtration. As an example
building blocks. Recently, we reported a one-pot synthe- we report the isolation of 3-cyano-7-hydroxy-2-imi-
sis under neat conditions and in aqueous medium of nocoumarin (4d) (see the experimental section).
chromene derivatives starting from 3-nitrocoumarins.2o
Here we report a new approach for synthesizing 3-
This process works well for preparing chloro- (6b), hy-
droxy- (6c, 6d, 6f), methoxy- (6e, 6h) substituted 3-car-
boxycoumarins and is very important for synthesizing
hydrophobic 3-carboxycoumarins, such as the 8- and 6,8-
tert-butyl derivatives 6g and 6i. The procedure is clean,
environmentally friendly and takes advantage of two as-
SYNTHESIS 2003, No. 15, pp 2331–2334
x
x.
x
x
.
2
0
0
3
Advanced online publication: 23.09.2003
DOI: 10.1055/s-2003-41061; Art ID: T04603SS.pdf
Georg Thieme Verlag Stuttgart · New York
©

2
332
F. Fringuelli et al.
Table 1 Synthesis of 3-Cyano- and 3-Carboxycoumarins in Water
Entry Aldehyde 1 3-Cyanocoumarin 5 3-Carboxycoumarin 6
PAPER
added and the mixture was heated at 90 °C under stirring for the
time (t ) reported in Table 1. The sodium salts of 3-carboxycou-
marins are soluble in H O. The final solution, cooled to r.t., was
3
2
Yield (%)e
acidified with concd HCl to pH 2 under stirring and refrigerated at
0–5 °C. 3-Carboxycoumarins 6 were separated from the aqueous
medium by vacuum-filtration using a Büchner funnel under reduced
pressure and then dried (yield 60–95%), The crude coumarins had a
purity higher than 98% which could be further purified by recrystal-
lization.
R
t1
(
t2
(h)
Yield t3
h)a
b
(%)c
(h)d
a
b
c
d
e
f
H
2
2.5
2
90
95
85
85
95
85
84
90
95
2
90
85
80
85
95
85
60
90
89
6-Cl
4f
4
2
6-OH
7-OH
7-OMe
8-OH
8-t-Bu
1
3
-Cyanocoumarin (5a)11
3
Mp 180-182 °C (EtOH).
IR (KBr): 2220 (C≡N), 1730 (C=O), 1615 cm–1 (C=C).
1H NMR 400 MHz (DMSO-d6): = 7.46 (apparent t, 1 H, H-6,
J = 7.6 Hz), 7.50 (d, 1 H, H-8, J = 8.0 Hz), 7.76–7.84 (m, 2 H, H-5,
5
2
2
3
2
5
2.5
1g
2
2.5
4
7
), 8.94 (s, 1 H, H-4).
g
h
1.5
2
+
MS: m/z (%) = 51 (5), 63 (8), 88 (14), 143 (100) 171 (M , 97).
5,7-(OMe)2 4f
1g
8i
3
-Carboxycoumarin (6a)15
i
6,8-(t-Bu)2 6h
1.5
Mp 186–188 °C (EtOAc).
IR (KBr): 1750 (C=O), 1690 (C=O), 1615 cm–1 (C=C).
a
At r.t. and pH 8.3.
At 90 °C and under acid conditions.
Yield of isolated compound.
At 90 °C and pH 8.3 followed by acidification.
Overall yield of isolated compound.
At pH 12.4.
At pH 13.3.
At pH 13.3 and in H O–MeOH (9:1).
At pH 9.0.
b
c
d
e
f
1H NMR 400 MHz (DMSO-d6): = 7.39 (apparent t, 1 H, H-6,
J = 7.5 Hz), 7.43 (d, 1 H, H-8, J = 8.2 Hz), 7.72 (ddd, 1 H, H-7,
J = 8.2, 7.5, 1.5 Hz), 7.90 (dd, 1 H, H-5, J = 7.7, 1.5 Hz), 8.74 (s, 1
H, H-4).
g
h
i
MS: m/z (%) = 45 (9), 62 (9), 63 (17), 89 (34), 90 (20), 145 (20), 146
+
(100), 190 (M , 29).
2
6
-Chloro-3-cyanocoumarin (5b)14
Mp 191–192 °C (EtOH).
pects of using aqueous medium: (i) several reactions can
be performed in sequence by simply changing the pH of IR (KBr): 2242 (C≡N), 1735 (C=O), 1614 cm–1 (C=C).
the reaction medium and (ii) the desired products 4, 5 and
1H NMR 200 MHz (acetone-d6): = 7.49 (d, 1 H, H-8, J = 8.9 Hz),
6
can be isolated by filtration without having to use any 7.81 (dd, 1 H, H-7, J = 8.9, 2.6 Hz), 7.92 (d, 1 H, H-5, J = 2.6 Hz),
organic solvent.
8.75 (s, 1 H, H-4).
1
MS: m/z (%) = 63 (8), 75 (5), 87 (10), 114 (51), 149 (10), 177 (76),
All of the compounds prepared were characterized by H
NMR, IR and GC-MS analyses and are described in the
experimental section.
3
5
+
37
+
1
79 (26), 205 ( Cl – M , 100), 207 ( Cl – M , 34).
3
-Carboxy-6-chlorocoumarin (6b)17
Mp 240 °C (dec.).
IR (KBr): 3189 (OH), 1743 (C=O), 1678 (C=O), 1620 cm–1 (C=C).
The coumarins 5g, 6g, 5i and 6i and the iminocoumarin 4d are new
1
1
13
14
11
11
11
16
compounds. The 3-cyanocoumarins 5a, 5b, 5c, 5d, 5e, 5f,
1H NMR 200 MHz (DMSO-d
): = 7.44 (d, 1 H, H-8, J = 8.9 Hz),
.74 (dd, 1 H, H-7, J = 8.9, 2.6 Hz), 8.02 (d, 1 H, H-5, J = 2.6 Hz),
1
1
15
16
17
18
6
and 5h and the 3-carboxycoumarins 6a, 6b, 6c, 6d, 6e,
6
7
8
f, and 6h16 are known compounds, but since their spectroscopic
1
9
.66 (s, 1 H, H-4).
data are often missing, all of the coumarins prepared are described
here. The IR spectra were recorded with a FT Perkin-Elmer RXI
spectrometer in KBr and with a FT Bruker IFS 113V spectrometer
as CsI pellets. NMR spectra were recorded on FT Bruker AC 200
and FT Bruker DRX 400 instruments in DMSO-d and acetone-d
3
-Cyano-6-hydroxycoumarin (5c)13
Mp 237–238 °C (H O–EtOH).
2
IR (KBr): 3213 (OH), 2236 (C≡N), 1719 (C=O), 1615 cm–1 (C=C).
1H NMR 200 MHz (DMSO-d6): = 7.15–7.35 (m, 3 H, H-5, 7, 8),
6
6
solution. GC-MS analyses were performed with an HP 6890 GC
System–HP 5973 Mass Selective Detector. All starting materials
are commercially available.
8
.65 (s, 1 H, H-4), 9.07 (OH).
3
-Carboxy-6-hydroxycoumarin (6c)16
3
-Carboxycoumarins 6 and Their Precursors 4 and 5
Mp 283 °C (EtOH).
IR (KBr): 3149 (OH), 1728 (C=O), 1650 (C=O), 1615 cm–1 (C=C).
1H NMR 200 MHz (DMSO-d6): = 7.15–7.33 (m, 3 H, H-5, 7, 8),
A suitable salicylaldehyde 1 (10 mmol), malononitrile (2) (0.80 g,
1
0
2.5 mmol) and 0.05 M aq NaHCO solution (pH 8.3, 50 mL) or
3
.025 M aq NaOH solution (pH 12.4, 50 mL) or 0.2 M aq NaOH so-
lution (pH 13.3, 50 mL) were vigorously stirred at r.t. in a 100 mL
round-bottom flask fitted with a mechanical or magnetic stirrer and
8.65 (s, 1 H, H-4).
reflux condenser for the time (t ) reported in Table 1. 3-Cyano-2-
iminocoumarins 4 were separated by vacuum filtration or conc. HCl
3-Cyano-7-hydroxy-2-iminocoumarin (4d)
1
Mp 250 °C (dec.) (DMF–H O, 9:1).
2
(
1.25–2.0 mL) was added and the heterogeneous mixture was heat-
IR (CsI pellet): 3261 (NH), 3094 (OH), 3049 (C=C–H), 2230
ed at 90 °C under stirring for 1–2.5 h (t of Table 1). After cooling,
2
–1
(
C≡N), 1660 (C=NH), 1619, 1560 (C=C), 1252 cm (C–O).
3
-cyanocoumarins 5 were separated by vacuum filtration or 1 M aq
NaHCO solution (20 mL) or 1.5 M aq NaOH solution (20 mL) was
3
Synthesis 2003, No. 15, 2331–2334 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of 3-Carboxycoumarins
2333
1
13
H NMR 400 MHz (DMSO-d ): = 6.51 (d, 1 H, H-8, J = 2.1 Hz),
C NMR 200 MHz (acetone-d ): = 29.9, 35.4, 102.6, 114.8,
6
6
6
8
.67 (dd, 1 H, H-6, J = 8.5, 2.1 Hz), 7.40 (d, 1 H, H-5, J = 8.5 Hz),
.20 (s, 1 H, H-4); 8.57 (br s, 1 H, NH), 10.86 (br s, 1 H, OH).
118.9, 125.9, 129.1, 133.6, 138.5, 154.1, 154.4, 157.0.
MS: m/z (%) = 63 (3), 77 (4), 91 (3), 101 (2), 115 (4), 128 (7), 140
13C NMR 400 MHz (DMSO-d6): = 102.0, 109.7, 112.7, 115.8,
1
(6), 156 (8), 172 (4), 184 (90), 185 (13), 212 (100), 213 (18), 227
+
31.1, 146.1, 146.9, 155.1, 155.8, 163.6.
(M , 30).
Anal. Calcd for C H NO : C, 73.99; H, 5.77; N, 6.16. Found: C,
-Cyano-7-hydroxycoumarin (5d)11
14
13
2
3
7
3.90; H, 5.79; N, 6.17.
Mp 273–275 °C (H O–AcOH, 9:1).
2
IR (CsI pellet): 3237 (OH), 3042 (C=C–H), 2236 (C≡N), 1704
(
8-tert-Butyl-3-carboxycoumarin (6g)
C=O), 1618, 1610, 1565 (C=C), 1274 cm– (C–O).
1
Mp 180–181 °C (EtOH–H O).
2
1
IR (KBr): 3174 (OH), 1761 (C=O), 1735 (C=O), 1618 cm–1 (C=C).
H NMR 400 MHz (DMSO-d ): = 6.77 (d, 1 H, H-8, J = 2.2 Hz),
6
6
8
.88 (dd, 1 H, H-6, J = 8.6, 2.2 Hz), 7.63 (d, 1 H, H-5, J = 8.6 Hz),
.77 (s, 1 H, H-4), 11.31 (br s, 1 H, OH).
1H NMR 200 MHz (acetone-d6): = 1.51 (s, 9 H, t-C H ), 7.46 (t, 1
H, H-6, J = 7.8 Hz), 7.82 (dd, 1 H, H-5, J = 7.8, 1.6 Hz), 7.88 (d, 1
H, H-7, J = 7.8, 1.6 Hz), 8.92 (s, 1 H, H-4).
4
9
13C NMR 400 MHz (DMSO-d6): = 96.1, 102.5, 110.3, 114.6,
1
15.2, 131.8, 153.3, 156.6, 157.5, 164.8.
13C NMR 200 MHz (DMSO-d6):
28.7, 131.5, 136.5, 149.3, 153.1, 156.3, 163.9.
= 29.4, 34.5, 117.4, 118.4, 124.4,
1
3
-Carboxy-7-hydroxycoumarin (6d)18
MS: m/z (%) = 63 (3), 77 (4), 91 (5), 115 (14), 128 (11), 159 (18),
Mp 248–250 °C (dec.) (H O–AcOH, 8:2).
2
+
1
87 (4), 203 (12), 213 (59), 231 (100), 232 (16), 246 (M , 30).
IR (CsI pellet): 3178 (OH, COOH), 3059 (C=C–H), 1720 (C=O),
1
–
1
Anal. Calcd for C H O : C, 68.28; H, 5.73. Found: C, 68.31; H,
685 (C=O), 1617, 1560 (C=C), 1217 cm (C–O).
14 14
4
5
.76.
1
H NMR 400 MHz (DMSO-d ): = 6.72 (d, 1 H, H-8, J = 2.2 Hz),
6
6
8
.83 (dd, 1 H, H-6, J = 8.6, 2.2 Hz), 7.73 (d, 1 H, H-5, J = 8.6 Hz),
-Cyano-5,7-dimethoxycoumarin (5h)11
Mp 233–235 °C (acetone).
IR (KBr): 2220 (C≡N), 1710 (C=O), 1610 cm–1 (C=C).
1H NMR 200 MHz (DMSO-d6): = 3.09 (s, 3 H, OCH ), 3.92 (s, 3
3
.67 (s, 1 H, H-4), 11.15 (br s, 1 H, OH), 12.70 (br s, 1 H, CO H).
2
13C NMR 400 MHz (DMSO-d6): = 101.8, 110.7, 112.5, 114.1,
1
32.0, 149.4, 157.0, 157.7, 164.0, 164.3.
3
-Cyano-7-methoxycoumarin (5e)11
Mp 217–218 °C (EtOH–acetone).
H, OCH ), 6.57 (d, 1 H, H-8, J = 2.0 Hz), 6.68 (d, 1 H, H-6, J = 2.0
Hz), 8.68 (s, 1 H, H-4).
3
3
IR (KBr): 2220 (C≡N), 1730 (C=O), 1605 cm–1 (C=C).
-Carboxy-5,7-dimethoxycoumarin (6h)16
Mp 238–240 °C (EtOH).
3
1H NMR 200 MHz (acetone-d6): = 4.00 (s, 3 H, OCH ), 6.95–7.15
3
(m, 2 H, H-6, 8), 7.75 (br d, 1 H, H-5, J = 8.6 Hz), 8.63 (s, 1 H, H-4).
IR (KBr): 3350 (OH), 1740 (C=O), 1690 (C=O), 1615 cm–1 (C=C).
MS: m/z (%) = 51 (5), 75 (8), 88 (5), 102 (17), 130 (15), 158 (66),
1
H NMR 200 MHz (DMSO-d6): = 3.88 (s, 3 H, OCH ), 3.93 (s, 3
+
3
1
73 (69) 201 (M , 100).
H, OCH ), 6.51 (d, 1 H, H-8, J = 2.0 Hz), 6.60 (d, 1 H, H-6, J = 2.0
3
Hz), 8.68 (s, 1 H, H-4).
3
-Carboxy-7-methoxycoumarin (6e)16
Mp 192–193 °C (EtOH)
IR (KBr): 3320 (OH), 1740 (C=O), 1700 (C=O), 1620 cm–1 (C=C).
6
,8-Di-tert-Butyl-3-cyanocoumarin (5i)
Mp 143–144 °C (EtOH).
1H NMR 200 MHz (acetone-d6): = 4.01 (s, 3 H, OCH ), 7.06–7.16
IR (KBr): 2233 (C≡N), 1744 (C=O), 1615 cm–1 (C=C).
1H NMR 200 MHz (acetone-d6): = 1.37 (s, 9 H, t-C H ), 1.50 (s,
3
(m, 2 H, H-6, 8), 7.94 (br d, 1 H, H-5, J = 8.6 Hz), 8.88 (s, 1 H, H-4).
4
9
+
MS: m/z (%) = 50 (30), 77 (37), 133 (100), 176 (95), 220 (M , 51).
9 H, t-C H ), 7.72 (d, 1 H, H-5, J = 2.4 Hz), 7.84 (d, 1 H, H-7,
4 9
J = 2.4 Hz), 8.74 (s, 1 H, H-4).
3
-Cyano-8-hydroxycoumarin (5f)11
13
C NMR 200 MHz (acetone-d ): = 30.0, 31.4, 35.3, 35.7, 102.4,
6
Mp 244–245 °C (H O–EtOH).
IR (KBr): 3216 (OH), 2230 (C≡N), 1716 (C=O), 1610 cm–1 (C=C).
1H NMR 200 MHz (DMSO-d6): = 7.23 (m, 3 H, H-5, 6, 7), 8.84
2
1
14.9, 118.6, 125.3, 131.4, 138.0, 148.5, 152.3, 154.8, 157.2.
MS: m/z (%) = 57 (12), 77 (1), 91 (1), 112 (3), 127 (3), 212 (12), 224
(2), 240 (23), 268 (100), 269 (29), 283 (M , 24).
+
(
s, 1 H, H-4), 10.40 (OH).
-Carboxy-8-hydroxycoumarin (6f)19
Anal. Calcd for C H NO : C, 76.29; H, 7.47; N, 4.94. Found: C,
1
8
21
2
7
6.35; H, 7.46; N, 4.96.
3
Mp 282–284 °C (BuOH).
IR (KBr): 3150 (OH), 1730 (C=O), 1650 (C=O), 1615 cm–1 (C=C).
6
,8-Di-tert-butyl-3-carboxycoumarin (6i)
Mp 268–270 °C (dec.).
1
IR (KBr): 3418 (OH), 1734 (C=O), 1710 (C=O), 1620 cm–1 (C=C).
H NMR 200 MHz (DMSO-d ): = 7.1–7.4 (m, 3 H, H-5, 6, 7), 8.65
6
(s, 1 H, H-4).
1
H NMR 200 MHz (DMSO-d ): = 1.30 (s, 9 H, t-C H ), 1.44 (s, 9
6
4
9
H, t-C H ), 7.50 (d, 1 H, H-5, J = 2.3 Hz), 7.63 (d, 1 H, H-7, J = 2.3
Hz), 8.24 (s, 1 H, H-4)
4
9
8
-tert-Butyl-3-cyanocoumarin (5g)
Mp 145–147 °C (EtOH).
IR (KBr): 2238 (C≡N), 1740 (C=O), 1615 cm–1 (C=C).
1H NMR 200 MHz (acetone-d6): = 1.49 (s, 9 H, t-C H ), 7.41 (t, 1
H, H-6, J = 7.8 Hz), 7.71 (dd, 1 H, H-5, J = 7.8, 1.6 Hz), 7.79 (d, 1
H, H-7, J = 7.8, 1.6 Hz), 8.77 (s, 1 H, H-4).
1
3
C NMR 200 MHz (DMSO-d ): = 29.4, 31.0, 38.9, 40.1, 118.5,
6
1
20.2, 124.3, 127.6, 135.7, 146.2, 147.0, 150.8, 157.8, 165.0.
4
9
MS: m/z (%) = 57 (7), 77 (1), 91 (1), 115 (3), 128 (4), 187 (3), 213
+
(
9), 243 (4), 258 (3), 269 (12), 287 (100), 288 (20), 302 (M , 20).
Synthesis 2003, No. 15, 2331–2334 © Thieme Stuttgart · New York

2
334
F. Fringuelli et al.
PAPER
Anal. Calcd for C H O : C, 71.50; H, 7.33. Found: C, 71.58; H,
(6) Bonsignore, L.; Cottiglia, F.; Lavagna, S. M.; Loy, G.; Secci,
18
22
4
7
.29.
D. Heterocycles 1999, 50, 469.
(
(
7) Fomine, S.; Rivera, E.; Fomina, L.; Ortiz, A.; Ogawa, T.
Polymer 1998, 39, 3551.
8) (a) Neat, ZnO catal., 80 °C, H : Rouessac, F.; Lecler, A.
Acknowledgment
+
+
Synth. Commun. 1993, 23, 1147. (b) In DMF, r.t., H :
The Ministero dell’Istruzione dell’Università e della Ricerca (MI-
UR) and the Università degli Studi di Perugia are thanked for finan-
cial support.
Amstrong, V.; Soto, O.; Valderrama, J. A.; Tapia, R. Synth.
Commun. 1998, 18, 717. (c) Neat, EPZG/EPZ10 catal.,
MW: Bandgar, B. P.; Uppalla, L. S.; Curule, D. S. Green
Chem. 1999, 1, 243. (d) Neat NH OAc, r.t. or in H O,
4
2
NH OAc, r.t.: Scott, J. L.; Raston, C. L. Green Chem. 2000,
References
4
2
, 245. (e) Neat, LiClO or LiBr, MW: Bandgar, B. P.;
4
(1) Murray, R. D. H.; Mendez, J.; Brown, S. A. The Natural
Coumarins; Wiley: New York, 1982.
Uppalla, L. S.; Sadavarte, V. S. J. Chem. Res., Synop. 2002,
40. (f) In H O, reflux: Maggi, R.; Bigi, F.; Carloni, S.;
2
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