Preparation of 4,6,3',4'-tetrasubstituted aurones via aluminium oxide-catalyzed condensation

Article abstract of DOI:10.1002/jhet.5570420721

4,6,3',4'-Tetrasubstituted aurones were prepared by a protection- deprotection route with an alumina-catalyzed condensation of 3(2H)-benzofuranones with substituted aldehydes as the key step. Aureusidin (6) was obtained by demethylation of 4,6,3',4'-tetramethoxyaurone (5), a natural product from Cyperus capitatus. 4,6,3',4'-Tetrabenzyloxyaurone (9) was converted in a one hydrogenation-deprotection step to dihydroaureusidin (10).

Full text of DOI:10.1002/jhet.5570420721

Preparation of 4,6,3',4'-Tetrasubstituted Aurones via Aluminium
Oxide-Catalyzed Condensation
Nov-Dec 2005
1399
David Bolek and Michael Gütschow*
Pharmaceutical Institute, Poppelsdorf, University of Bonn, Kreuzbergweg 26, D-53115 Bonn, Germany
Received May 2, 2005
4,6,3',4'-Tetrasubstituted aurones were prepared by a protection-deprotection route with an alumina-cat-
alyzed condensation of 3(2H)-benzofuranones with substituted aldehydes as the key step. Aureusidin (6)
was obtained by demethylation of 4,6,3',4'-tetramethoxyaurone (5), a natural product from Cyperus capita-
tus. 4,6,3',4'-Tetrabenzyloxyaurone (9) was converted in a one hydrogenation-deprotection step to dihy-
droaureusidin (10).
J. Heterocyclic Chem., 42, 1399 (2005).
Aurones and auronols are naturally occurring 3(2H)-
an intermediate of the quercetin degradation by the human
intestinal bacterium Eubacterium ramulus [9]. We have
recently reported on the synthesis of 2-benzyl-2-hydroxy-
benzofuran-3(2H)-one, the prototype of naturally occur-
ring auronols [10]. Besides aureusidin (6), 4,6,3',4'-
tetramethoxyaurone (5) was isolated from the rhizomes of
Cyperus capitatus [11]. Herein, we describe a facile syn-
thetic route to 4,6,3',4'-tetrasubstituted aurones including
the closely related dihydroaureusidin (10), which has not
been reported as a secondary plant metabolite thus far.
Main synthetic pathways to aurones are (i) via an oxida-
tive ring closure of 2'-hydroxychalcones [1], e.g. by Algar-
Flynn-Oyamada reaction [12], (ii) from α-halogen-β-
alkoxy-dihydrochalcones (Wheeler reaction) [13], (iii) by
silver(I) ion- or tetrakis(triphenylphosphine)palladium-
catalyzed cyclization of phenylethinyl-(2-hydroxyphenyl)
ketones [14], and (iv) condensation of benzofuran-3(2H)-
ones with substituted benzaldehydes. The latter method
was used for the syntheses presented in this report.
Following a report of Beney et al. [15], condensation of
phloroglucinol with chloroacetonitrile was catalyzed by
zinc chloride to give the iminium intermediate 1 in 52 %
yield. We have isolated and characterized this salt, and
nmr data (e.g. three distinct OH signals) revealed that the
corresponding atoms of the trihydroxyphenyl substituent
were not equivalent. This can be explained by a hydrogen
bond interaction between the iminium nitrogen and the
hydroxy oxygen of the phenyl group. The iminium salt 1
was hydrolyzed with aqueous hydrochloric acid to provide
a 1:1 mixture of the acetophenone derivative 2 and its
cyclized form, the benzofuranone 3. The mixture was
treated with sodium methoxide to quantitatively produce 3.
An analytical sample of 2 was separated from the mixture
and showed equivalent nmr signals at positions 2, 6 and 3,
5 of the phenyl group, respectively. Treatment of 3 with
methyl iodide yielded the protected benzofuranone 4.
4,6,3',4'-Tetramethoxyaurone (5) was readily prepared
in 73 % yield by condensation of 4 with 3,4-dimethoxy-
benzaldehyde on an alumina surface, according to a
methodology of Varma and Varma [16]. The reaction was
carried out in the dark in order to prevent a light-induced
benzofuranone derivatives, biogenetically related to chal-
cones. Aurones, 2-benzylidene-3(2H)-benzofuranones,
represent a group of plant products which are structurally
isomeric to flavones. Aurones have a limited occurrence
in fruits and vegetables and confer bright yellow color to
flowers such as Antirrhinum, Cosmos, and Coreopsis. In
recent years, these compounds have received much atten-
tion, due to their promising biological activities.
Noteworthy, in several cases aurones were reported to be
more active than the equally substituted chalcone and
flavone derivatives [1].
The affinity of aurones, particularly 4-hydroxy-6-
methoxyaurones, towards the C-terminal nucleotide-bind-
ing domain of P-glycoprotein was reported [2]. Among
several flavonoids tested for their ability to modulate P-
glycoprotein-mediated multidrug resistance in vitro, 4,6-
dimethoxyaurone exhibited a potent reversing activity [3].
Aurones have also been designed to mimic flavopiridol, an
inhibitor of cyclin-dependent kinases, and derivatives with
4-piperidinyl moieties at position 7 were more potent and
selective than flavopiridol itself [4]. Several aurones
showed a strong inhibition of rat liver microsomal type I
iodothyronine deiodinase [5]. Moreover, aurones could be
regarded as conformationally restricted analogues of
bioactive chalcones, such as α-methyl-3-hydroxy-
4,3',4',5'-tetramethoxychalcone, a potent inhibitor of tubu-
lin polymerization [6]. Sulfuretin, 6-hydroxy-2-(3,4-dihy-
droxybenzylidene)-3(2H)-benzofuranone, a naturally
occurring aglycon isolated from Cotinus was found to be a
potent antioxidant in a free-radical scavenging assay [7].
The biosynthesis of aurones includes the oxidative
cyclization of corresponding chalcones, a process that is
catalyzed by aureusidin synthase [8]. Aureusidin (6) is the
best known aurone and has been isolated from several
species of Cyperus. Aureusidin shares the hydroxy substi-
tution pattern with the frequently cited flavonol quercetin,
whose glycosides are highly abundant dietary flavonoids,
the dihydroflavonol taxifolin, and the auronol alphitonin
(= 2,4,6-trihydroxy-2-(3,4-dihydroxybenzyl)-3(2H)-ben-
zofuranone). The latter compound has been identified as

1400
D. Bolek and M. Gütschow
Vol. 42
Scheme 1
isomerization. As reported, the isolation of 5 from
Cyperus capitatus led to a mixture of the (E)- and more
stable (Z)-form which could not be separated [11]. The
procedure described herein, exclusively yielded the pure
Demethylation of 5 to afford aureusidin (6) turned out to
be difficult. A complete deprotection with boron tribro-
mide (eight equivalents) was not attained and traces of a
monomethylated byproduct had to be removed by recrys-
tallization. Boumendjel et al. [2] reported on a selective
demethylation at position 4 of 4,6-dimethoxyaurones using
two equivalents boron tribromide in methylene chloride.
The benzofuranone 3 was also converted to the protected
form 7. Reaction of 3 with benzyl bromide afforded a prod-
uct mixture which was fractionated by column chromatog-
raphy to obtain 7. The further synthetic route to dihydroau-
reusidin (10) involved the preparation of 3,4-dibenzyloxy-
benzaldehyde (8) and its condensation with 7 to produce
the tetrabenzyloxy derivative 9 in 73 % yield. Again, this
reaction was accomplished in the presence of basic alu-
minum oxide in a minimum amount of methylene chloride.
The approach to combine hydrogenation and deprotection
1
13
(Z)-isomer, as determined by H and
C nmr spectra.
The values are consistent with those present in the litera-
ture for (Z)-aurones [10,11,15]. The assignment is mainly
based on differences in the shift of the olefinic proton
being around 6.70 ppm for the (Z)- and around 7.00 ppm
for the (E)-isomer. It is also in agreement with literature
data on the chemical shift of the C-2' hydrogen of 5 with a
significantly lower value for the (Z)-isomer (δ = 7.55 ppm)
than for the (E)-isomer (δ = 8.48 ppm) [11]. Accordingly,
the nmr spectra of the tetrabenzyl derivative 9 (δ = 6.62
ppm, -CH=) revealed the occurrence of the (Z)-form.
However, thin-layer chromatograms of 5 and 9 showed
two spots indicating the aforementioned isomerization.

Nov-Dec 2005
Preparation of 4,6,3',4'-Tetrasubstituted Aurones
1401
mately 27 mmoles) was added to a solution of sodium methoxide
prepared from sodium (2.1 g, 91.3 mmoles) and methanol (50
ml). The red solution was refluxed over 2 hours and became vio-
let. After evaporation under reduced pressure, the residue was
partitioned between 1 M hydrochloric acid (180 ml) and ethyl
acetate (60 ml). Insoluble material was separated by filtration and
was pure product 3. The aqueous phase was extracted with ethyl
acetate (3 × 60 ml), the organic layers were combined, washed
with water (90 ml) and brine (90 ml), dried over sodium sulfate
and evaporated to dryness to obtain additional pure product 3 as a
light-brown solid. Yield 4.0 g (89 %), mp 253-256 °C, ref 210-
into a one step to obtain the benzyl derivative 10 was suc-
cessful. The reaction was performed on palladium/charcoal
in tetrahydrofuran at room temperature, and only a single
recrystallization was required to obtain the desired dihy-
droaureusidin (10). In the light of the biological activities
of analogously substituted flavonoids, an evaluation of the
potential of compound 10 appears particularly promising.
EXPERIMENTAL
1
212 °C [15], 250-256.6 [17]; H nmr (DMSO-d ): δ 4.53 (s, 2H,
6
Melting points were obtained on a Rapido Boetius apparatus
and are uncorrected. The ir spectra were recorded on Bruker
CH ), 5.90, 5.92 (each d, J = 1.85 Hz, 2H, H-5 and -7), 10.53,
2
13
10.54 (each s, total 2H, OH); C nmr (DMSO-d ): δ 74.9 (C-2),
90.3, 96.4 (C-5, C-7), 102.8 (C-3a), 157.6, 167.7, 175.8 (C-4, C-
6, C-7a), 194.1 (CO).
6
1
Tensor 27 FT-IR spectrometer. H nmr spectra (500 MHz) and
13
C nmr spectra (125 MHz) were recorded on a Bruker Avance
instrument. Mass spectra (70 eV) were obtained on a MS-50
A.E.I spectrometer. Elemental analyses were performed on a
Vario EL apparatus. Thin-layer chromatography was carried out
4,6-Dimethoxy-3(2H)-benzofuranone (4).
Methyl iodide (12.8 g, 5.6 ml, 90 mmoles) was added to a mix-
ture of 3 (5.0 g, 30 mmoles), potassium carbonate (8.3 g, 60
mmoles) and dimethylformamide (75 ml). The mixture was
stirred at 80 °C for 1 hour. It was evaporated under reduced pres-
sure, and the residue was partitioned between water (150 ml) and
ethyl acetate (150 ml). Insoluble material was separated by fil-
tration and was crude product 4. The aqueous phase was
extracted with ethyl acetate (1 × 150 ml, 2 × 60 ml), the organic
layers were combined, washed with water (100 ml) and brine
(100 ml), dried over sodium sulfate and evaporated to dryness to
obtain additional crude product 4. The combined crude material
was recrystallized from ethyl acetate to obtain 2.6 g (45 %) of 4
using aluminum sheets coated with silica gel 60 F
(Merck).
254
Chromatograms were detected by UV fluorescence and visual-
ized with FeCl (in 0.5 M hydrochloric acid) or I /KI (in
3
2
ethanol/water 1:10) and 2 N hydrochloric acid. Column chro-
matography was performed with silica gel 60 G (Merck).
2-(2-Chloro-1-iminoethyl)-1,3,5-benzenetriol hydrochloride (1).
A solution of phloroglucinol (25.2 g, 200 mmoles) in anhy-
drous diethyl ether (125 ml) was prepared at 0 °C.
Chloroacetonitrile (15.1 g, 200 mmoles), freshly glowed zinc
chloride (0.9 g, 6.6 mmoles) and subsequently a solution of
hydrogen chloride in anhydrous diethyl ether (1 M, 375 ml) was
added. The mixture was stirred at 0 °C for 3 hours and additional
21 hours at room temperature. The precipitate was removed by
filtration, washed with anhydrous diethyl ether (2 × 40 ml) and
dried to give 24.8 g (52%) of 1 as a yellow solid, mp 230-233 °C;
1
as yellow crystals, mp 132-136 °C, ref [15] 132-133 °C; H nmr
(DMSO-d ): δ 3.81, 3.84 (each s, total 6H, CH ), 4.64 (s, 2H,
6
3
13
CH ), 5.88, 6.02 (each d, J = 1.7 Hz, 2H, H-5 and –7); C nmr
2
(DMSO-d ): δ 55.9, 56.3 (CH ), 75.4 (C-2), 89.5, 93.0 (C-5, C-
6
3
7), 104.2 (C-3a), 158.4, 169.4, 176.4 (C-4, C-6, C-7a), 194.0
(CO).
1
H nmr (DMSO-d ): δ 5.44 (s, 2H, CH ), 6.08, 6.32 (each d, J =
6
2
+
1.9 Hz, 2H, H-3 and -5), 7.52 (s, 2H, NH ), 9.87, 10.96, 12.59
(each s, total 3H, OH); C nmr (DMSO-d ): δ 76.1 (CH ), 90.9,
97.9 (Ph C-3 and -5), 100.2 (Ph C-1), 161.3, 173.8, 174.5, 176.7
2
13
(Z)-2-[(3,4-Dimethoxyphenyl)methylene]-4,6-dimethoxy-3(2H)-
benzofuranone (5).
6
2
+
(C=NH , Ph C-2, -4 and -6).
2
Aluminum oxide (65 g; activated, basic, type 5016A
Brockmann I) was added to a solution of 4 (3.88 g, 20 mmoles)
and 3,4-dimethoxybenzaldehyde (3.99 g, 24 mmoles) in methyl-
ene chloride (40 ml). The mixture was thoroughly stirred for 16
hours at room temperature under exclusion of light. The suspen-
sion was filtered off, the residue was washed with methylene
chloride (4 × 130 ml) and the washes were combined with the fil-
trate. The solvent was evaporated and the residue recrystallized
from methylene chloride/methanol 1:1 to give 5.0 g (73 %) of 5
Anal. Calcd. for C H Cl NO : C, 40.36; H, 3.81; N, 5.88.
8
9
2
3
Found: C, 39.99; H, 3.82; N, 5.92.
2-Chloro-1-(2,4,6-trihydroxyphenyl)ethanone (2).
A mixture of the salt 1 (23.8 g, 100 mmoles) and 1 M
hydrochloric acid (500 ml) was refluxed for 1 hour. The red solu-
tion was kept at 0 °C overnight, and the precipitate was collected
by filtration, washed with ice-cold water (20 ml) and thoroughly
dried in vacuo over phosphorus pentoxide to give 13.4 g of a
mixture of the compounds 2 and 3 (in a relation of approximately
1
as a yellow solid, mp 163-167 °C, ref [18] 169-170 °C; H nmr
(deuteriochloroform): δ 3.89, 3.91, 3.93, 3.94 (each s, total 12H,
1
1:1 as determined by H nmr). This mixture can be used without
CH ), 6.11, 6.33 (each d, J = 1.9 Hz, 2H, H-5 and -7), 6.71 (s, 1H,
3
purification in the next step. The material was recrystallized
three times from ethanol/water to obtain 1.0 g (5%) of 2 as a col-
orless solid, mp 207-208 °C, conversion 184-203 °C, ref [15]
CH), 6.89 (d, J = 8.5 Hz, 1H, H-5'), 7.42 (dd, J = 8.5, 1.9 Hz, 1H,
13
H-6'), 7.44 (d, J = 1.9 Hz, 1H, H-2'); C nmr (deuteriochloro-
form): δ 55.92, 55.94, 56.1, 56.2 (CH ), 89.1, 93.9 (C-5, C-7),
3
1
185-187 °C; H nmr (DMSO-d ): δ 4.96 (s, 2H, CH ), 5.83 (s,
6
2
105.4 (C-3a), 111.16, 111.23, 113.6 (CH, C-2', C-5'), 125.3 (C-
6'), 125.5 (C-1'), 146.8, 149.0, 150.3 (C-2, C-3', C-4'), 159.4,
168.70, 168.73 (C-4, C-6, C-7a), 180.5 (CO).
13
2H, Ph H-3 and -5), 10.49 (s, 1H, OH), 12.03 (s, 2H, OH);
C
nmr (DMSO-d ): δ 51.0 (C-2), 94.9 (Ph C-3 and -5), 102.7 (Ph
6
C-1), 164.1 (Ph C-2 and -6), 165.6 (Ph C-4), 194.8 (CO).
Anal. Calcd. for C
H O : C, 66.66; H, 5.30. Found: C,
19 18 6
66.48; H, 5.36.
4,6-Dihydroxy-3(2H)-benzofuranone (3).
A mixture of 2 and 3 (in a molar relation of approximately 1:1)
was prepared as described above. This mixture (5 g, approxi-
(Z)-2-[(3,4-Dihydroxyphenyl)methylene)-4,6-dihydroxy-3(2H)-
benzofuranone (6).

1402
D. Bolek and M. Gütschow
Vol. 42
A Schlenk tube containing compound 5 (1.03 g, 3 mmoles)
(Z)-2-[(3,4-Dibenzyloxyphenyl)methylene]-4,6-dibenzyloxy-
3(2H)-benzofuranone (9).
was evacuated and flushed with argon. Anhydrous methylene
chloride (25 ml) was injected via septum. A solution of boron tri-
bromide (6.0 g, 2.3 ml, 24 mmoles) in anhydrous methylene
chloride (10 ml) was injected at 0 °C. The mixture was stirred for
3 hours at this temperature and for additional 21 hours at room
temperature. Ice-water (30 ml) was carefully added, it was
stirred for 5 minutes and the precipitate was separated by suction
filtration. The crude product was recrystallized from
methanol/water 1:1 to obtain 0.31 g (36%) of compound 6 as an
orange solid. This material contains a monomethoxy compound
(δ = 3.83 ppm) as an impurity. An analytic sample was obtained
by repeated recrystallization from ethyl acetate, mp 285-290 °C,
Aluminium oxide (19.5 g; activated, basic, type 5016A
Brockmann I) was added to a solution of 7 (2.08 g, 6 mmoles) and
3,4-dibenzyloxybenzaldehyde 8 (2.87 g, 9 mmoles) in methylene
chloride (12 ml). The mixture was thoroughly stirred for 12
hours at room temperature under exclusion of light. The suspen-
sion was filtered off, the residue was washed with methylene
chloride (4 × 60 ml) and the washes were combined with the fil-
trate. The solvent was evaporated and the residue recrystallized
from methylene chloride/methanol 1:1 to give 2.30 g (73 %) of 9
as a yellow solid, mp 157-160 °C; ir (potassium bromide) ν 1684
-1 1
(C=O), 1616, 1595, 1512 (C=C), 1246, 1091 (C-O) cm ; H nmr
1
conversion 235-240 °C, ref [19] 265-270 °C; H nmr (DMSO-
(DMSO-d ): δ 5.21, 5.22, 5.27, 5.28 (each s, total 8H, OCH Ph),
6
2
d ): δ 6.05, 6.16 (each d, J = 1.6 Hz, 2H, H-5 and -7), 6.43 (s, 1H,
6
6.54, 6.78 (each d, J = 1.9 Hz, 2H, H-5 and -7), 6.62 (s, 1H, CH),
7.16 (d, J = 8.5 Hz, 1H, H-5'), 7.28-7.50 (m, 21H, Ph), 7.64 (d, J
CH), 6.80 (d, J = 8.2 Hz, 1H, H-5'), 7.16 (dd, J = 8.2, 2.0 Hz, 1H,
H-6'), 7.37 (d, J = 2.0 Hz, 1H, H-2'), 9.15, 9.49, 10.76, 10.78
13
= 2.2 Hz, 1H, H-2'); C nmr (DMSO-d ): δ 70.1, 70.2, 70.3, 70.7
6
13
(each s, total 4H, OH); C nmr (DMSO-d ): δ 90.4, 97.8 (C-5,
6
(CH ), 91.01, 96.50 (C-5, C-7), 104.8 (C-3a), 110.1 114.4, 116.7
2
C-7), 103.0 (C-3a), 109.7, 116.1, 117.7 (CH, C-2', C-5'), 123.8
(C-1'), 124.0 (C-6'), 145.6, 146.0, 147.6 (C-2, C-3', C-4'), 158.3,
167.1, 167.7 (C-4, C-6, C-7a), 179.2 (CO).
(CH, C-2', C-5'), 125.2 (C-6'), 125.4 (C-1'), 127.6, 127.73,
127.74, 128.2, 128.5, 128.56, 128.62, 128.7 (C-2'', C-3'', C-2''',
C-3''', C-2'''', C-3'''', C-2''''', C-3'''''), 127.95, 128.01, 128.1, 128.4
(C-4'', C-4''', C-4'''', C-4'''''), 136.1, 136.4, 137.0, 137.2 (C-1'', C-
1''', C-1'''', C-1'''''), 146.4, 148.2, 150.0 (C-2, C-3', C-4'), 158.0,
167.7, 168.0 (C-4, C-6, C-7a), 179.0 (CO); ms: (70 ev) m/z 646
4,6-Dibenzyloxy-3(2H)-benzofuranone (7).
Benzyl bromide (11.29 g, 7.85 ml, 66 mmoles) was added to a
mixture of compound 3 (4.98 g, 30 mmoles), potassium carbon-
ate (9.12 g, 66 mmoles) and dimethylformamide (100 ml). The
mixture was stirred at 80 °C for 1 hour, and the solvent was
removed under reduced pressure. The residue was partitioned
between ethyl acetate (150 ml) and water (100 ml). The aqueous
layer was extracted with ethyl acetate (1 × 150 ml, 2 × 60 ml).
The combined organic layers were washed with water (100 ml)
and brine (100 ml), dried over sodium sulfate and evaporated to
dryness. The crude material was purified by column chromatog-
raphy (petroleum ether/ethyl acetate 1:1) to yield 2.8 g (27 %) of
+
(38%, M ), 91 (100%).
Anal. Calcd. for C
H O : C, 79.86; H, 5.30. Found: C,
43 34 6
79.90; H, 5.30.
2-[(3,4-Dihydroxyphenyl)methyl]-4,6-dihydroxy-3(2H)-benzo-
furanone (10).
A Schlenk flask containing 10% Pd/C (260 mg, 0.24 mmoles)
was evacuated and flushed with argon. The flask was provided
with hydrogen, a solution of 9 (970 mg, 1.5 mmoles) in anhy-
drous tetrahydrofuran (70 ml) was injected via septum, and the
mixture was stirred at room temperature. After 24 hours, the
reaction was stopped by filtration of the catalyst. The filtrate was
evaporated, and the brown oil was recrystallized from
methanol/water 1:4 to give 190 mg (44 %) of 10 as a colorless
solid, mp 244-247 °C; ir (potassium bromide) ν 3473, 3292 (O-
1
7 as colorless crystals, mp 102-103 °C, ref [20] 105-106 °C; H
nmr (deuteriochloroform): δ 4.85 (s, 2H, CH ), 5.03, 5.19 (each
2
s, total 4H, OCH Ph), 6.09, 6.20 (each d, J = 2.9 Hz, 2H, H-5 and
2
13
-7), 7.27-7.44 (m, 10H, Ph); C nmr (deuteriochloroform): δ
70.4, 70.7 (CH Ph), 75.6 (C-2), 90.3, 95.2 (C-5, C-7), 105.4 (C-
2
3a), 126.7, 127.6, 127.9, 128.5, 128.6, 128.7 (Ph), 135.5, 136.0
(C-1', C-1''), 157.8, 168.5, 177.0 (C-4, C-6, C-7a), 194.7 (CO).
-1
1
H), 1669 (C=O), 1610, 1596 (C=C), 1339, 1222 (C-O) cm ; H
nmr (DMSO-d ): δ 2.65 (dd, J = 14.8, 8.2 Hz, 1H, CH ), 2.97
6
2
(dd, J = 14.8, 3.8 Hz, 1H, CH ), 4.68 (dd, J = 8.2, 3.8 Hz, 1H, H-
3,4-Dibenzyloxybenzaldehyde (8).
2
2), 5.84, 5.86 (each d, J = 1.6 Hz, 2H, H-5, H-7), 6.47 (dd, J = 7.9,
2.2 Hz, 1H, H-6'), 6.58 (d, J = 7.9 Hz, 1H, H-5'), 6.62 (d, J = 2.2
Hz, 1H, H-2'), 8.62, 8.69, 10.48, 10.50 (each s, total 4H, OH);
Benzyl bromide (11.29 g, 7.85 ml, 66 mmoles) was added to a
mixture of 3,4-dihydroxybenzaldehyde (4.14 g, 30 mmoles),
potassium carbonate (9.12 g, 66 mmoles) and dimethylformamide
(100 ml). The mixture was stirred overnight at room temperature.
It was evaporated under reduced pressure, and the residue was
partitioned between water (50 ml) and ethyl acetate (50 ml). The
aqueous layer was extracted with ethyl acetate (1 × 50 ml, 2 × 25
ml), the organic layers were combined, washed with water (50 ml)
and brine (50 ml) and dried over sodium sulfate. The volume was
reduced in vacuo to 30 ml and poured into petroleum ether (150
ml). The precipitate was collected by filtration and recrystallized
from ethanol/water 9:1 to give 3.8 g (40 %) of 8 as colorless crys-
13
C nmr (DMSO-d ): δ 36.4 (CH ), 85.9, 90.1, 96.2 (C-2, C-5,
6
2
C-7), 102.6 (C-3a), 115.5, 116.9 (C-2', C-5'), 120.1 (C-6'), 127.4
(C-1'), 144.0, 145.0 (C-3', C-4'), 157.7, 167.8, 174.3 (C-4, C-6,
+
C-7a), 194.8 (CO); ms: (70 ev) m/z 288 (56%, M ), 166 (100%).
Anal. Calcd. for C
H O : C, 62.50; H, 4.20. Found: C,
15 12 6
62.31; H, 4.54.
Acknowledgement.
D. B. thanks the Erasmus Program for financial support.
1
tals, mp 85-87 °C, ref [21] 85-86 °C; H nmr (DMSO-d ): δ 5.21,
6
5.27 (each s, total 4H, OCH Ph), 7.27-7.54 (m, 13H, Ph), 9.81 (s,
REFERENCES AND NOTES
2
13
1H, CHO); C nmr (DMSO-d ): δ 70.1 (CH ), 112.3, 113.5 (C-2,
6
2
C-5), 126.3 (C-6), 127.6, 127.7, 128.5, 128.6 (C-2', C-2'', C-3', C-
3''), 128.0, 128.1 (C-4', C-4''), 130.0 (C-1), 136.7, 137.0 (C-1', C-
1''), 148.6 (C-3), 153.8 (C-4), 191.4 (CO).
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