Microwave assisted one pot synthesis of 7-substituted 2-(2-oxo-2H-chromen-3-yl)acetic acids as precursors of new anti-tumour compounds

Article abstract of DOI:10.2478/s11696-010-0059-x

Perkin condensation with subsequent intramolecular lactonisation as one pot syntheses of 2-(2-oxo-2H-chromen-3-yl)acetic acids VIIa-Xa has been studied. The required acids VIIa-Xa were prepared as precursors of recently discovered compounds possessing antineoplastic activities. Syntheses of VIIa-Xa were carried out using para substituted 2-hydroxybenzaldehydes II-VI, succinic acid anhydride, sodium succinate under thermal or microwave conditions. Significant shortening of the reaction time under microwave irradiation was observed (18-50 min instead of 1.5-5 h of heating). Microwave assisted reactions proceeded more smoothly to give higher yield of the required products VIIa-Xa (31-61 %) compared to those under classical thermal conditions e.g. 21.8 % for IXa (Hurenkamp et al., 2007). Seven reaction by-products were isolated and determined as 2H,2′H-3,3′-bichromene-2,2′-diones VIIb-Xb and (E)-3-(2-hydroxystyryl)-2H-chromen-2-ones VIIc-IXc.

Full text of DOI:10.2478/s11696-010-0059-x

Chemical Papers 64 (6) 806–811 (2010)
DOI: 10.2478/s11696-010-0059-x
ORIGINAL PAPER
Microwave assisted one pot synthesis of 7-substituted
2-(2-oxo-2 -chromen-3-yl)acetic acids as precursors
of new anti-tumour compounds
Silvia Kováčová, Lucia Kováčiková, Margita Lácová, Andrej Boháč*,
Marta Sališová
Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University,
Mlynská dolina, 842 15 Bratislava, Slovakia
Received 3 February 2010; Revised 17 May 2010; Accepted 21 May 2010
Perkin condensation with subsequent intramolecular lactonisation as one pot syntheses of 2-
(2-oxo-2H-chromen-3-yl)acetic acids VIIa–Xa has been studied. The required acids VIIa–Xa were
prepared as precursors of recently discovered compounds possessing antineoplastic activities. Syn-
theses of VIIa–Xa were carried out using para substituted 2-hydroxybenzaldehydes II–VI, succinic
acid anhydride, sodium succinate under thermal or microwave conditions. Significant shortening of
the reaction time under microwave irradiation was observed (18–50 min instead of 1.5–5 h of heat-
ing). Microwave assisted reactions proceeded more smoothly to give higher yield of the required
products VIIa–Xa (31–61 %) compared to those under classical thermal conditions e.g. 21.8 % for
IXa (Hurenkamp et al., 2007). Seven reaction by-products were isolated and determined as 2H,2ꢀH-
3,3ꢀ-bichromene-2,2ꢀ-diones VIIb–Xb and (E)-3-(2-hydroxystyryl)-2H-chromen-2-ones VIIc–IXc.
c
ꢀ 2010 Institute of Chemistry, Slovak Academy of Sciences
Keywords: microwave, coumarine, Perkin condensation, Perkin lactonisation, anti-cancer com-
pounds, fluorescence
Introduction
The aim of this work was to find convenient and
optimal conditions for the preparation and purifica-
tion of VIIa–Xa and all reaction by-products.
Development of new antineoplastic compounds is
highly required because of yearly increasing amount of
cancer events (National Cancer Institute, 2010). Re-
cently, several new compounds with the leading skele-
ton (L) have been prepared (Fig. 1). Their anticancer
activities were determined on the sixty human tumour
cell lines assay in NCI USA (GI50: 10−6–10−8 M)
(NCI/NIH, 2010). The particular mechanism of their
cytostatic influence is not yet known. Their structures
and biological activities were described by Lácová &
Boháč (2006). Skeleton (L) represents a conjugated
system of two aromatic rings and three double bonds
that allow studying the relationship between biological
activities and electron distributions within the possi-
ble push–pull system. Structures and syntheses of new
lead compounds (L) are depicted in Fig. 1.
Experimental
Resorcinol (I ), 3-(N,N-dimethylamino)phenol (II )
and Zn(CN)2 were purchased from Sigma–Aldrich
(Germany). Hexanes is a commercially available mix-
ture of nonpolar solvents (light fraction of hydrocar-
bons from petrol), b.p. 45–65◦C. Condensation re-
actions were performed in a Microwave oven Sencor
SMW5020 (USA), 800W, 2450 MHz, with power regu-
lation. Solvents were dried and purified using conven-
tional methods. DMF was dried by distillation from
CaH2 · POCl3, and distilled prior to use. All reactions
were carried out under argon atmosphere. TLC was
performed on Merck F254 silica gel precoated on alu-
*Corresponding author, e-mail: andrej.bohac@fns.uniba.sk

S. Kováčová et al./Chemical Papers 64 (6) 806–811 (2010)
807
OR2
O
O
O
R1
O
R
O
L
O
O
O
CHO
R1
HO
R
O
O
VIIa−Xa
HO
OH
OH
HO
R1
R1
R
R
O
O
I, II
III−VI
R: H⎯, HO⎯, MeO⎯, Me2N⎯
Fig. 1. Convergent synthesis of compounds L requiring the preparation of 2-(2-oxo-2H-chromen-3-yl)acetic acids VIIa–Xa from
3-substituted phenols. Optimal meta position of substituents R and R1 was chosen for the best electronic influence on the
possible push–pull system in L.
mina plates. For the spots detection, a UV lamp (254
nm) and I2 vapours were used. Melting points (m.p.)
were determined on a Kofler hot stage and are un-
corrected. Simple distillations were performed on a
Bu¨chi KGR apparatus. FTIR spectra were recorded
as solid samples on a FTIR-ART REACT IR 1000
(ASI Applied Systems, UK) instrument in the region
of 650–4002 cm−1. Elemental analyses (C, H, N) were
obtained by a Carlo Erba Strumentazione Model 1106
analyzer (Italy). 1H NMR and 13C NMR spectra were
recorded on a Varian Gemini (USA) (300 MHz for
1H or 75.4 MHz for 13C) spectrometer in CDCl3 or
DMSO-d6. Chemical shifts based on TMS and cou-
pling constants (J ) are in Hz. HETCOR, HMQC,
COSY, or NOE techniques were used for exact spec-
tral assignments. Compounds VIIb–Xb were not solu-
ble enough even in warm DMSO and their 13C NMR
and FTIR spectra could not be recorded.
H2O, CHCl3 and dried on air (371.4 mg, 1.28 mmol,
13.6 %). The water solution was extracted with CHCl3
(6 × 20 mL). CHCl3 was chosen as the solvent because
it dissolves VIIa and VIIc but not the excess suc-
cinic acid. Combined CHCl3 solution was extracted
with saturated aqueous Na2CO3 (4 × 20 mL). The
by-product VIIc was separated from the evaporated
CHCl3 organic layer and purified by flash chromatog-
raphy (SiO2, hexanes : EtOAc, ϕr = 0.5) (99.4 mg,
0.38 mmol, 4.0 %). The basic water phase was sepa-
rated, acidified by 10 % HCl (30 mL) and extracted
with EtOAc (3 × 70 mL). The combined ethyl ac-
etate layer was dried over Na2SO4, filtered and evap-
orated on rotary evaporator. 2-(2-Oxo-2H-chromen-
3-yl)acetic acid (VIIa) was obtained (2.35 g, 11.51
mmol, 61.2 %) as ochreous powder. Crude acid VIIa
was purified by crystallisation from hot H2O. The re-
sult was comparable to those presented in literature
(60 % yield after 5 h at 185◦C (Ito, 1951) or 57 %
after 1.5 h of reflux in (Et)3N (Bochkov et al., 2008)).
2-(2-Oxo-2H-chromen-3-yl)acetic acid (VIIa) is a yel-
low crystalline compound with m.p. of 154.0–158.0◦C
(H2O); 157.5◦C (Ito, 1951). 2H,2ꢀH-3,3ꢀ-Bichromene-
2,2ꢀ-dione (VIIb) is a pale yellow powder with m.p.
of 319.0–323.0◦C; 315.0◦C (Dey & Sankaranarayanan,
1931). 3-(2-Hydroxystyryl)-2H-chromen-2-one (VIIc)
is a yellow crystalline compound with m.p. of 208.0–
213.0◦C (FLC); 207.0◦C (Dey & Sankaranarayanan,
1931).
General procedure for preparation of VIIa–Xb
Synthesis of VIIa–VIIc by condensation of salicy-
laldehyde (III ) with succinic acid anhydride was per-
formed as follows. A mixture of salicylaldehyde III
(2.30 g, 18.83 mmol), succinic acid anhydride (9.42
g, 94.13 mmol) and sodium succinate (4.06 g, 25.05
mmol) in absolute DMF (5.00 mL) was heated in a
microwave oven at 250 W (9 × 2 min) until com-
plete consumption of salicylaldehyde III (determined
by TLC: SiO2, hexanes : EtOAc, ϕr = 0.5, RF = 0.71).
Afterwards, the mixture was acidified with 10 % HCl
(20 mL) and stirred at room temperature for 30 min
to allow the hydrolysis of the excess succinic acid an-
hydride. Insoluble 2H,2ꢀH-3,3ꢀ-bichromene-2,2ꢀ-dione
(VIIb) was filtered off, washed with small amounts of
The above procedure was used also for other start-
ing aldehydes. The conditions and yields are shown
in Table 1. Characterisation and spectral data of the
newly prepared compounds are given in Tables 2 and
3, respectively.
Condensation of 2,4-dihydroxylbenzaldehyde (IV)

808
S. Kováčová et al./Chemical Papers 64 (6) 806–811 (2010)
Table 1. Reaction conditions and obtained product yields for different starting aldehydes
Microwave
Product yieldb/%
Aldehyde
Succinic acid anhydride to
Na2(OOCCH2)2 mole ratio
Power/W
Time/min
a
b
c
IIIa
IVc
Vd
5.00 : 1.33
4.00 : 1.33
4.00 : 1.33
4.00 : 1.33
250
350
350
500
9 × 2
6 × 2
VII
VIII
IX
61
31
40
31
14
9
12
0.4
4
0.5
3
10 × 3
10 × 5
VIe
X
0
a) Only in this case 5 mL of DMF per 18.8 mmol of starting aldehyde III were used, other reactions were carried out under solvent
free conditions; b) reactions were performed in scale from 3.0 mmol to 18.8 mmol of the starting aldehydes (corresponding to 0.5–2.3
g of the appropriate aldehydes); c) mixture was carefully melted by a hot melt gun just before microwave irradiation, crude solid
product could be extracted by CHCl3 in a Soxhlet apparatus overnight instead of the extraction using water solution, pre-purified
product VIIIa was contaminated with succinic acid which was removed by an in situ conversion at 175◦C under HV to volatile
succinic acid anhydride that sublimed off the mixture on a Bu¨chi KGR apparatus. Crude solid material left after the sublimation
was crystallised from the mixture of H2O/EtOH; d) reaction mixture was melted by a hot melt gun before microwave irradiation;
e) conversion of VI was not better even if higher excess of succinic acid anhydride or prolonged microwave irradiation were used. In
such case more polymeric material was produced. Basic properties of product Xa (containing Me2N— group) had to be considered
by its isolation and pH had to be carefully adjusted in the range of 5–6 for its successful precipitation from the water solution.
with succinic acid anhydride: The obtained prod-
ucts: 2-(7-Hydroxy-2-oxo-2H-chromen-3-yl)acetic acid
(VIIIa) white crystalline compound. M.p. 217.0–
220.0◦C (H2O / EtOH). 7,7ꢀ-Dihydroxy-[3,3ꢀ]bichrom-
enyl-2,2ꢀ-dione (VIIIb) ocherous powder. M.p. 296.0–
298.0◦C (DMSO / H2O). 18 % yield from 7-hydro-
xycoumarine by oxidative coupling with FeCl3 at
50◦C within 2 h (Reisch & Zappel, 1992). 3-(2,4-
crowave assisted reactions proceeded more smoothly
and they provided higher yields of the required prod-
ucts VIIa–Xa compared to those obtained by ther-
mal syntheses. Significant shortening of the reaction
time under microwave irradiation was recorded (18–
50 min instead of 1.5–5 h under common heating).
Convenient isolation of products VIIa–Xa by acid-
base extraction is described. Structures of all ob-
Dihydroxystyryl)-7-hydroxy-2H-chromen-2-one(VIIIc) served by-products VIIb–Xb and VIIc–IXc were de-
yellow crystalline compound, m.p. 250.0–252.5◦C (H2O termined. By-products 2H,2ꢀH-3,3ꢀ-bichromene-2,2ꢀ-
/EtOH).
Condensation of 2-hydroxy-4-methoxybenzalde-
diones VIIb–Xb were formed subsequently from VIIa–
Xa by additional condensation with the appropriate
aldehydes III–VI followed by dehydration of inter-
mediates. Intermadiates 3,3ꢀ-bichromene-2,2ꢀ-diones
VIIb–Xb were not soluble enough even in warm
DMSO and therefore some of their spectra could not
be recorded. Formation of (E)-3-(2-hydroxystyryl)-
7-methyl-2H-chromen-2-ones VIIc–IXc was expected
during high temperature decarboxylation of interme-
diates (Fig. 2).
para Substituted salicylaldehydes IV–VI were pre-
pared from resorcinol (I ) or 3-(dimethylamino)phenol
(II ). 2,4-Dihydroxybenzaldehyde (IV) was prepared
in a 68 % yield by the Gattermann–Adams formyla-
tion from resorcinol (I ), Zn(CN)2 and HCl (g) (Fig. 3)
(Adams & Levin, 1923) as the Vilsmeier–Haack formy-
lation of I is less advantageous (Vilsmeier & Haack,
1927). In case of the latter, lower yield (50 %) and
hyde (V ) with succinic acid anhydride was per-
formed. Obtained products were: 2-(7-methoxy-2-oxo-
2H-chromen-3-yl)acetic acid (IXa), ocherous crys-
talline compound with m.p. of 179.0–182.0◦C (decom-
posing) (H2O/EtOH); 177.5–177.9◦C (H2O/EtOH)
(Hurenkamp et al., 2007), 7,7ꢀ-dimethoxy-[3,3ꢀ]bi-
chromenyl-2,2ꢀ-dione (IXb), pale yellow powder with
m.p. of 293–294◦C (DMSO) (Lele et al., 1961), and 3-
(2-hydroxy-4-methoxystyryl)-7-methoxy-2H-chromen-
2-one (IXc), yellow crystalline powder with m.p. of
250.0◦C (decomposing) (FLC).
Condensation of 4-(dimethylamino)-2-hydroxy-
benzaldehyde (VI ) with succinic acid anhydride was
done and products: 2-(7-N,N-dimethylamino-2-oxo-
2H-chromen-3-yl)acetic acid (Xa), yellow crystalline
compound with m.p. of 190.0–195.0◦C (acetone/H2O),
and 7,7ꢀ-N,N-dimethylamino-[3,3ꢀ]bichromenyl-2,2ꢀ-dione also O-formylated by-products were observed.
(Xb), pale yellow crystalline compound with m.p. of
Selective monomethylation of 2,4-dihydroxybenz-
aldehyde (IV ) by KHCO3/MeI was used to synthe-
sise 2-hydroxy-4-methoxybenzaldehyde (V ) in a 60 %
yield (Binnemans et al., 2000). The observed regiose-
lectivity was explained by different ability of KHCO3
to abstract protons from the two hydroxyl groups of
IV. The hydroxy group in para position is more acidic
compared to that in the ortho position. Product V was
selectively isolated from the crude mixture by tritura-
tion in hexanes. Nonpolar hexanes did not solve the
230.0◦C (decomposing) (DMSO/H2O), were obtained.
Results and discussion
One pot syntheses of 2-(2-oxo-2H-chromen-3-yl)-
acetic acids VIIa–Xa starting from para substituted
2-hydroxybenzaldehydes III–VI, succinic acid anhy-
dride, and sodium succinate carried out by microwave
irradiation are described. It was observed that mi-

S. Kováčová et al./Chemical Papers 64 (6) 806–811 (2010)
809
succinic anhydride
sodium succinate
R
O
O
R
O
R
O
OH
HO
+
H
COOH
MW
O
HOOC
Intermediate
(250−500 W, 18−50 min)
VIIa−Xa
R
III
R:
H
OH
IV
V
− CO2
− H2O
OCH3
N(CH3)2 VI
R
O
R
O
O
O
HO
VIIc−IXc
R
O
O
R
VIIb−Xb
Fig. 2. Proposed mechanism for the formation of desired products VIIa–Xa and all observed reaction by-products VIIb–Xb, VIIc–
IXc and their yields.
1.00 mol eq.
OH
2.00
1.00 mol eq.
1.50 / 1.50
HO
OH MeI, KHCO3
acetone
OH
HO
O
a/ HCl (g), Zn(CN)2, 0 °C
b/ H2O, 100 °C, 30 min
H
CHO
reflux, 72 h
c/ crystallisation EtOH / H2O
O
I
IV, 68 %
V, 60 %
Fig. 3. Synthesis of 2,4-dihydroxybenzaldehyde (IV ) under Adams conditions and 2-hydroxy-4-methoxybenzaldehyde (V ) by
methylation of IV.
1.00 mol eq.
OH
4.81, 1.79
N
O
OH
N
OH
N
a/ DMF, POCl3, 0 °C−r.t.
O
b/ 100 °C, 30 min
c/ FLC (Hexsol : EtOAc)
O
II
VI, 66 %
VIa, 3 %
Fig. 4. Synthesis of 4-(dimethylamino)-2-hydroxybenzaldehyde (VI) and VIa under Vilsmeier–Haack conditions.
Table 2. Characterisation data of newly prepared compounds
wi(calc.)/%
wi(found)/%
Compound
Formula
Mr
Yield/%
M.p./◦C
C
H
N
–
VIIIc
IXc
Xa
C17H12O5
C19H16O5
296.27
324.33
247.25
376.41
68.92
69.03
70.36
70.62
63.15
63.07
70.20
70.32
4.08
4.15
4.97
5.02
5.30
5.42
5.36
5.42
0.5
3
250.0–252.5
250.0a
–
C13H13NO4
C22H20N2O4
5.67
5.51
7.44
7.32
31
0.4
190.0–195.0
230.0a
Xb
a) Decomposing.
polar starting aldehyde IV (Fig. 3).
Synthesis of 4-(dimethylamino)-2-hydroxybenzal-
dehyde (VI ) was performed by the Vilsmeier–Haack
formylation. The reaction gave product VI in a 66 %
yield. A small amount of by-product VIa was also ob-
tained (Fig. 4).

810
S. Kováčová et al./Chemical Papers 64 (6) 806–811 (2010)
Table 3. Spectral data of newly prepared compounds
Compound Spectral data
VIIaa
IR, ν˜/cm−1: 3300–2366 (br m, COOH), 1722 (s, C O), 1691 (s, C O), 1610 (m, C C), 1455 (m), 1428 (m), 1390
—
—
—
—
—
—
(m), 1343 (m), 1289 (w), 1243 (s, C—O from lactone), 1189 (m), 1116 (w), 1073 (m), 919 (br m), 853 (w), 787 (m),
749 (s), 664 (w)
1H NMR (DMSO-d6), δ: 12.53 (br s, 1 H, COOH), 7.99 (s, 1 H, H-4), 7.70 (dd, 1 H, J5,6 = 7.7 Hz, J5,7 = 1.6 Hz,
H-5), 7.61 (ddd, 1 H, J7,8 = 8.3 Hz, J6,7 = 7.0 Hz, J5,7 = 1.6 Hz, H-7), 7.42 (dm, 1 H, J7,8 = 8.3 Hz, w1/2 ≈ 2.5
Hz, among others J6,8 = 1.2 Hz, H-8), 7.37 (ddd, 1 H, J5,6 = 7.7 Hz, J6,7 = 7.0 Hz, J6,8 = 1.2 Hz, H-6), 3.51 (s, 2
H, CH2COO)
13C NMR (CDCl3), δ: 169.0 (s, COOH), 161.5 (s, C-2), 153.5 (s, C-9), 142.0 (d, C-4), 131.6 (d, C-7), 127.8 (d, C-5),
124.6 (d, C-6), 121.9 and 119.0 (2 × s, C-3 and C-10), 116.7 (d, C-8), 35.9 (t, CH2)
VIIba
VIIca
1H NMR (DMSO-d6), δ: 8.44 (s, 2 H, H-4), 7.83 (dd, 2 H, J5,6 = 7.8 Hz, J5,7 = 1.5 Hz, H-5), 7.43 (ddd, 2 H, J5,6
= 7.8 Hz, J6,7 = 7.3 Hz, J6,8 = 1.0 Hz, H-6), 7.69 (ddd, 2 H, J7,8 = 8.3 Hz, J6,7 = 7.3 Hz, J5,7 = 1.5 Hz, H-7),
7.49 (dm, 2 H, J7,8 = 8.3 Hz, w1/2 ≈ 2.5 Hz, among others J6,8 = 1.0 Hz, H-8)
1H NMR (DMSO-d6), δ: 9.93 (s, 1 H, HO—), 8.26 (s, 1 H, H-4), 7.85 (d, 1 H, J11,12 = 16.9 Hz, H-12 or H-11), 7.76
(dd, 1 H, J5,6 = 7.6 Hz, J5,7 = 1.7 Hz, H-5), 7.59 (ddd, 1 H, J7,8 = 8.2 Hz, J6,7 = 7.4 Hz, J5,7 = 1.7 Hz, H-7),
7.56 (dd, 1 H, J17,18 = 7.9 Hz, J16,18 = 1.5 Hz, H-18), 7.42 (dm, 1 H, J7,8 = 8.2 Hz, w1/2 = 2.0 Hz, among others
J6,8 = 1.1 Hz, H-8), 7.37 (ddd, 1 H, J5,6 = 7.6 Hz, J6,7 = 7.4 Hz, J6,8 = 1.1 Hz, H-6), 7.21 (d, 1 H, J11,12 = 16.9
Hz, H-11 or H-12), 7.15 (ddd, 1 H, J15,16 = 8.3 Hz, J16,17 = 7.1 Hz, J16,18 = 1.5 Hz, H-16), 6.90 (dd, 1 H, J15,16
= 8.3 Hz, J15,17 = 1.1 Hz, H-15), 6.84 (ddd, 1 H, J17,18 = 7.9 Hz, J16,17 = 7.1 Hz, J15,17 = 1.1 Hz, H-17)
13C NMR (DMSO-d6), δ: 159.7 (s, C-2), 155.5 (s, ipso C-14), 152.2 (s, ipso C-9), 137.0 (d, C-4), 131.1 (d, C-7),
129.4 (d, C-16), 128.4 (d, C-12), 128.2 (d, C-5), 126.9 (d, C-18), 124.6, 124.5, and 123.5 (C-6, C-10, and C-17), 121.5
(d, C-11), 119.6 and 119.4 (C-3 and C-13), 115.9 (d, C-15), 115.8 (d, C-8)
VIIIaa
IR, ν˜/cm−1: 3219 (w, OH), 2925 (m), 2865 (w), 1690 (s, C O), 1613 (s, C O), 1459 (m), 1578 (m), 1505 (w),
—
—
—
—
1378 (m), 1312 (m), 1258 (m), 1223 (m), 1154 (m), 1076 (w), 853 (m), 791 (m)
1H NMR (DMSO-d6), δ: not seen (1 H, COOH), 7.83 (s, 1 H, H-4), 7.49 (d, 1 H, J5,6 = 8.5 Hz, H-5), 6.79 (dd, 1
H, J5,6 = 8.5 Hz, J6,8 = 2.3 Hz, H-6), 6.72 (d, 1 H, J6,8 = 2.3 Hz, H-8), 3.41 (s, 1 H, CH2)
13
—
C NMR (DMSO-d6), δ: 171.7 (s, COOH), 161.1 (s, C(2) O), 160.8 (s, C-7), 154.8 (s, C-9), 142.1 (d, C-4), 129.3
—
(d, C-5), 118.3 (s, C-3), 113.3 (d, C-6), 111.5 (s, C-10), 102.0 (d, C-8), 35.7 (t, CH2)
VIIIba
VIIIc
1H NMR (DMSO-d6), δ: 8.26 (s, 2H, C-4), 7.60 (d, 2H, J5,6 = 8.5 Hz, C-5), 6.83 (dd, 2H, J5,6 = 8.5 Hz, J6,8 = 2.3
Hz, C-6), 6.77 (d, 2H, J6,8 = 2.3 Hz, C-8), not seen (2H, —OH)
IR, ν˜/cm−1: 3288 (br s, OH), 2925 (s), 2856 (m), 1671 (m), 1621 (m), 1459 (m), 1378 (w), 1258 (m), 1076 (br m),
1015 (br m)
1H NMR (DMSO-d6), δ: 10.80 (s, 2 H, 2 × —OH), 9.79 (s, 1 H, —OH), 8.42 (s, 1 H, H-4), 7.74 (d, 1 H, J5,6 = 8.5
Hz, H-5), 7.47 (d, 1 H, J5,6 = 8.5 Hz, H-6), 7.43 (s, 1 H, H-8), 6.97 (s, 1 H, w1/2 = 4.7 Hz, H-15), 6.90–6.74 (m, 4
H, H-11, H-12, H-17, and H-18) with higher order multiplicity
IXaa
IXba
IXc
IR, ν˜/cm−1: 3223 (m), 2922 (s), 2852 (s), 1709 (s, C O), 1613 (s, C O), 1567 (m), 1509 (m), 1455 (m), 1385 (m),
—
—
—
—
1354 (w), 1289 (m), 1242 (m), 1188 (m), 1157 (s), 1119 (w), 1069 (w), 1027 (m), 972 (w), 818 (w), 783 (w), 726 (w)
1H NMR (DMSO-d6), δ: 8.32 (s, 2 H, H-4), 7.69 (d, 2 H, J5,6 = 8.6 Hz, H-5), 7.04 (s, 2 H, H-8), 6.99 (d, 2 H, J5,6
= 8.6 Hz, H-6), 3.89 (s, 6 H, —OMe)
IR, ν˜/cm−1: 3624–3061 (br m), 2937 (w), 1710 (s, C O), 1613 (s), 1505 (w), 1444 (br w), 1262 (m), 1208 (w), 1158
—
—
(m), 1031 (m), 799 (m)
1H NMR (DMSO-d6), δ: 9.94 (s, 1 H, —OH), 8.13 (s, 1 H, H-4), 7.68 (d, 1 H, J11,12 = 16.6 Hz, H-11), 7.65 (d, 1
H, J5,6 = 8.7 Hz, H-5), 7.45 (d, 1 H, J17,18 = 9.5 Hz, H-18), 7.03 (d, 1 H, J11,12 = 16.6 Hz, H-12), 7.02 (d, 1 H,
J6,8 = 2.4 Hz, H-8), 6.97 (dd, 1 H, J5,6 = 8.7 Hz, J6,8 = 2.4 Hz, H-6), 6.46 (d, 1 H, J15,17 = 2.4 Hz, H-15), 6.45
(dd, 1 H, J17,18 = 9.5 Hz, J15,17 = 2.4 Hz, H-17), 3.86 (s, 3 H, MeO—C(7)), 3.73 (s, 3 H, MeO—C(16))
Xa
Xb
1H NMR (DMSO-d6), δ: 12.36 (br s, 1 H, COOH), 7.76 (s, 1 H, H-4), 7.43 (d, 1 H, J5,6 = 8.8 Hz, H-5), 6.73 (dd, 1
H, J5,6 = 8.8 Hz, J6,8 = 2.4 Hz, H-6), 6.57 (d, 1 H, J6,8 = 2.4 Hz, H-8), 3.39 (s, 2 H, CH2), 3.02 (s, 6 H, —N(Me)2)
13C NMR (DMSO-d6) HMQC also, δ: 171.9 (s, COOH), 161.6 (s, C-2), 155.3 (s, C-9), 152.5 (s, C-7), 142.3 (d, C-4),
128.6 (d, C-5), 115.6 (s, C-3), 109.3 (d, C-6), 108.3 (s, C-10), 97.1 (d, C-8), 39.1 (q, —N(Me)2), 35.7 (t, CH2)
1H NMR (DMSO-d6), δ: 8.21 (s, 2 H, H-4), 7.53 (d, 2 H, J5,6 = 8.9 Hz, H-5), 6.77 (dd, 2 H, J5,6 = 8.9 Hz, J6,8
=
2.4 Hz, H-6), 6.60 (d, 2 H, J6,8 = 2.4 Hz, H-8), 3.06 (s, 12 H, 2 × (Me)2N—)
a) Known compounds with listed spectral data not yet described in literature.
Synthesis of 2-(2-oxo-2H-chromen-3-yl)acetic acid
(VIIa) was performed starting from salicylaldehyde
(III) in DMF under microwave irradiation (9 × 2 min
at the power of 250 W) in a 61 % yield (Fig. 2). Mi-
crowave irradiation significantly accelerated the reac-
tion compared to 5 h of heating at 185◦C (Ito, 1951)
or 1.5 h reflux in (Et)3N (Bochkov et al., 2008). By-
products VIIb and VIIc were obtained in 14 % and
4 % yields, respectively. The time of irradiation was
optimised by monitoring the consumption of salicy-
laldehyde (III) using TLC analysis (Table 1).
Synthesis of 2-(7-hydroxy-2-oxo-2H-chromen-3-yl)-
acetic acid (VIIIa) started from 2,4-dihydroxybenz-
aldehyde (IV ) according to the above described pro-

S. Kováčová et al./Chemical Papers 64 (6) 806–811 (2010)
811
cedure for VIIa in a 31 % yield. In this reaction, no
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