Transformations of 4-oxo-4H-chromene-3-carbaldehyde under the action of FE(CO)5

Article abstract of DOI:10.1134/S1070428012030207

Transformations of 4-oxo-4H-chromene-3-carbaldehyde in the presence of pentacarbonyliron and HMPA in benzene and toluene were studied, and their probable mechanism was proposed. The structure of 3-(4-oxochroman-3-ylmethyl)- 4H-chromen-4-one was determined by spectral methods and X-ray analysis. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070428012030207

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 3, pp. 451–455. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © A.A. Ambartsumyan, T.T. Vasil’eva, O.V. Chakhovskaya, N.E. Mysova, V.A. Tuskaev, V.N. Khrustalev, K.A. Kochetkov, 2012,
published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 3, pp. 450–454.
Transformations of 4-Oxo-4H-chromene-3-carbaldehyde
under the Action of Fe(CO)5
A. A. Ambartsumyana, T. T. Vasil’evaa, O. V. Chakhovskayaa, N. E. Mysovaa, V. A. Tuskaevb,
V. N. Khrustaleva, and K. A. Kochetkova
a Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 119991 Russia
e-mail: const@ineos.ac.ru
b Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
Received June 18, 2011
Abstract—Transformations of 4-oxo-4H-chromene-3-carbaldehyde in the presence of pentacarbonyliron and
HMPA in benzene and toluene were studied, and their probable mechanism was proposed. The structure of
3-(4-oxochroman-3-ylmethyl)-4H-chromen-4-one was determined by spectral methods and X-ray analysis.
DOI: 10.1134/S1070428012030207
The chemistry of 3-substituted chromones has
vigorously developed since 1970s when a simple and
convenient procedure for the synthesis of 3-formyl-
chromone (I) according to Vilsmeier–Haack has been
proposed [1]. 3-Formylchromones are geminally ac-
tivated alkenes possessing three electrophilic centers
(C2, C4, and 3-C) [2], and they are capable of acting as
Michael acceptors, heterodienes, etc. In most cases,
nucleophilic attack takes two possible pathways:
1,4-addition at the C2 atom and 1,2-addition at the
electrophilic carbon atom in the 3-substituent [3].
3-Alkylchromones that cannot be obtained by direct
alkylation of chromones [4] and bis-chromones linked
at the 3-position [4, 5] attract strong interest from the
chemical and biological viewpoints. It is known that
diols derived from some natural compounds, e.g., of
the menthol and α-pinene series, exhibit high physio-
logical activity; some derivatives are tested as anti-
convulsant and anticancer agents [6]. Taking into ac-
count that reduction of aldehydes and ketones provides
a direct route to such monomeric and dimeric com-
pounds, we made an attempt to use Fe(CO)5 to trans-
form formylchromone I into the corresponding diol
III, as well as into difficultly accessible 3-methyl-4H-
chromen-4-one (IV). The system Fe(CO)5–HMPA was
used by us previously for the reduction of haloalkanes
[7] and diastereoselective synthesis of 1,2-diols [8] and
other compounds [9] from aromatic aldehydes. We
found that aldehyde I in the presence of Fe(CO)5–
HMPA undergoes unusual transformations leading to
3-(4-oxochroman-3-ylmethyl)-4H-chromen-4-one (II)
as the major reduction product. The reaction was
carried out in benzene at 80°C (reaction time 6 h).
Compound II was isolated by preparative thin-layer
chromatography on silica gel using petroleum ether
(bp 40–60°C)–ethyl acetate (10:1) as eluent. Com-
pound II was obtained previously in a poor yield as
by-product in the reactions of derivatives of aldehyde
I, 3-aminomethylidene- or 3-hydroxymethylidene-
chroman-4-ones with nucleophiles [10, 11]. The struc-
ture of II was determined by H NMR and IR spec-
troscopy, mass spectrometry, and X-ray analysis.
Figure shows the structure of molecule II and some
its geometric parameters. Molecule II consists of two
chromone fragments linked through a methylene
1
C6
C5
O4
C4
C3
C13
O12
C14
C15
C4A
C8A
O1
C7
C8
C11
C12A
C10
C16
C16A
C17
O17
C9
C2
Structure of the molecule of 3-(4-oxochroman-3-ylmethyl)-
4H-chromen-4-one (II) according to the X-ray diffraction
data. Bond lengths: O1–C2 1.358(2), O1–C8A 1.369(2),
C11–O12 1.412(2), O12–C12A 1.362(2) Å; bond angles:
C2O1C8A 117.8(2), C3C9C10 113.2(2), C11O12C12A 115.3(2)º.
451

AMBARTSUMYAN et al.
452
Scheme 1.
O
O
O
OH
Fe(CO)5, PhMe
a
OH
III
O
O
O
O
O
O
Fe(CO)5, HMPA, PhMe
Me
+
b
O
+
II
IV
O
O
O
O
CHO
O
V
O
O
O
HMPA, PhMe
I
c
O
O
VII
O
O
O
O
HMPA, PhH
+
OH
OH
d
O
VIII
IX
O
O
Fe(CO)5, HMPA, PhH
II
+
IV
+
e
O
O
VI
bridge. The bond lengths and bond angles therein are
very consistent with the corresponding parameters of
other chromone derivatives with known structure
[12, 13]. The 4H-chromen-4-one fragment is planar,
whereas the dihydropyran ring in the chromanone
fragment adopts a chair conformation where the C11
atom deviates by 0.582 Å from the plane formed by
the other atoms of the ring. The chromone fragments
are turned with respect to each other through a dihedral
angle of 74.0°. Intermolecular distances in the crystal-
line structure of II conform to the corresponding van
der Waals radii.
determined unambiguously. The structure of com-
pound II indicates that the most probable site of the
initial attack is the aldehyde carbonyl carbon atom. In
order to elucidate the mechanism of formation of com-
pound II we examined transformations of 4-oxo-4H-
chromene-3-carbaldehyde (I) under various conditions
and obtained a number of products II–IX (Scheme 1).
The results are collected in table. No compound II
was formed in the absence of Fe(CO)5 or HMPA; in
the presence of Fe(CO)5–HMPA, the same products,
compound II and 3-methyl-4H-chromen-4-one (IV),
were obtained at different ratios regardless of the sol-
vent. When the reaction was carried is benzene, com-
pound II was the major product, whereas compound
IV prevailed in toluene (Scheme 1, paths b and e). In
addition, small amounts of bis-chromone V and bis-
According to [14], 4-oxo-4H-chromene-3-carbalde-
hyde can react with nucleophiles at all three electro-
philic centers, so that in some cases the direction of the
initial attack and subsequent transformations cannot be
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TRANSFORMATIONS OF 4-OXO-4H-CHROMENE-3-CARBALDEHYDE
453
Transformations of 4-oxo-4H-chromene-3-carbaldehyde (I) in benzene and toluene in the presence of Fe(CO)5–HMPA
Run no.
Fe(CO)5
HMPA
Solvent
Benzene
Major product
Yield, %
Conversion of I,a %
1
2
3
4
5
6
7
+
+
+
–
+
+
–
+
+
–
+
–
+
+
II
10
09
09
05
09
22
08
45
40
20
10
40
60
20
Benzene–water, 1:1
Benzene
II
VII
VIII
III
IV
Benzene
Toluene
Toluene
Toluene
VII
a
The conversion of I was determined by weighing the products isolated from the reaction mixture (1H NMR monitoring).
chromanone VI were identified by mass spectrometry.
In the reaction of I with Fe(CO)5 in benzene in the
absence of HMPA we detected 3,3′-(ethene-1,2-diyl)-
bis(4H-chromen-4-one) (VII) (Scheme 1, c), while in
the presence of HMPA in benzene [without Fe(CO)5]
4-oxo-4H-chromene-3-carboxylic acid (VIII) and
3-hydroxymethyl-4H-chromen-4-one (IX) were
formed (Scheme 1, d), presumably as a result of dis-
proprotionation according to Tishchenko. The prop-
erties of compounds VIII and IX were consistent with
published data [15, 16]. Finally, diol III was detected
only in the reaction mixture obtained in toluene in the
presence of Fe(CO)5 (without HMPA; Scheme 1, a).
under these conditions. Compound I also failed to
react with an enamine, 3-dimethylamino-1-(2-hy-
droxyphenyl)prop-2-en-1-one. The reaction was car-
ried out at 80°C in homogeneous medium (3 h), but
compound II was not detected.
Our results led us to presume that compound II is
formed according to Scheme 2. Reactive aldehyde I in
a reducing medium (pentacarbonyliron in benzene) [7]
is converted into 3-hydroxymethylidenechroman-4-one
(X) [11] which undergoes aldol condensation followed
by dehydration and elimination of formyl group with
formation of intermediate compound XI, and double
bond migration in the latter leads to more stable com-
pound II [10].
The reaction in toluene gives only traces of II, for
the reduction of aldehyde I does not stop at the stage
of formation of compound XI but goes further to
methylchromone IV. Compound IV was synthesized
previously by reduction of 2-chlorochromone with zinc
in acetic acid [16] or via transformation of 2-bromo-
chromone into 2-phenylsulfanyl and 2-phenylsulfonyl
derivatives [4]. In the absence of HMPA it was also
possible to obtain diol III, which supports the scheme
proposed in [9]. Diol III was isolated (no yield was
given) as a mixture of meso-form and D- and L-stereo-
We previously showed an important role of water
traces in the Reformatsky reaction with pentafluoro-
benzaldehyde in toluene or benzene under the condi-
tions corresponding to the formation of dimer accord-
ing to Scheme 1 [8]. However, in the examined reac-
tions with aldehyde I the presence of water almost did
not affect the results (see table; run nos. 1, 2). In order
to estimate the role of HMPA, the reaction was carried
out in the presence of DMF. In this case, catalysis by
traces of dimethylamine could be expected due to
intermediate formation of enamine derivative of chro-
mone I [10, 11]. Nevertheless, no reaction occurred
Scheme 2.
O
O
OH
O
O
H
O
O
CHO
H
O
O
I
X
XI
O
O
O
O
II
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

AMBARTSUMYAN et al.
454
isomers in the reduction of aldehyde I with zinc in
acetic acid [17].
0.7 ml (4 mmol) of HMPA and 0.27 ml (2 mmol) of
Fe(CO)5 were added, and the mixture was heated for
6 h at 80°C, the progress of the reaction being moni-
tored following evolution of carbon(II) oxide and by
TLC (petroleum ether–ethyl acetate 10:1). When the
reaction was complete, the mixture was treated with
30 ml of 1 N hydrochloric acid and washed with water,
the organic phase was dried over MgSO4, and the
product was isolated by preparative TLC on 180×240-
mm glass plates [silica gel 60 PF254 containing 30% of
gypsum; petroleum ether (bp 40–60°C)–ethyl acetate,
10:1]. Yield 0.0306 g (10%), mp 120°C. IR spectrum
(mineral oil), ν, cm–1: 3061 (C–Harom); 2923, 2853
(C–H); 1685, 1633 (C=O); 1607, 1574, 1465 (C=C,
Thus we have demonstrated versatile reactivity of
aldehyde I in pentacarbonyliron-containing systems
which promote its transformations into various mono-
meric and dimeric products.
EXPERIMENTAL
The mass spectra were obtained on a Finnigan
1
SSQ-7000 mass spectrometer. The H NMR spectra
were measured on a Bruker WP-300 instrument at
300 MHz using CDCl3 as solvent; the chemical shifts
are given relative to tetramethylsilane. The IR spectra
were recorded on an IKS-20 spectrometer. Thin-layer
chromatography was performed on Silufol UV-254
plates (Merck). The products were isolated by prepara-
tive thin-layer chromatography on glass 180×240- and
200×200-mm plates coated with a layer of silica gel
60 PF254 containing 30% of gypsum (Merck). All
organic reagents were purified by distillation. Com-
mercial pentacarbonyliron (98%; from Fluka) was used
without additional purification.
1
C=Carom). H NMR spectrum, δ, ppm: 2.69–2.76 and
2.99–3.05 (2H, CCH2CH, AB part of ABX spin system,
JAX = 6.3, JBX = 6.3, JAB = 14.0 Hz), 3.16–3.26 (1H,
X part of ABX spin system, JAX = 5.0, JBX = 5.0, JAB
=
11.5 Hz), 6.93–7.03 m (2H, Harom), 7.38–7.49 m (3H,
H
arom), 7.63–7.69 m (1H, Harom), 7.86–7.89 q (1H,
arom), 7.97 s (1H, OCH), 8.20–8.23 q (1H, Harom).
H
Mass spectrum, m/z (Irel, %): 306 (6) [M]+, 185 (15)
[M – C7H4O2]+, 160 (60) [185 – C2H2]+, 147 (100)
[160 – CH2]+, 121 (12) [147 – C2H2]+, 92 (10) [121 –
CO]+, 65 (7) [92 – CO]+.
X-Ray analysis of a single crystal of compound II
was performed at the X-Ray Analysis Laboratory,
Institute of Organometallic Compounds, Russian Acad-
emy of Sciences. Crystallographic data: C19H14O4;
M 306.30; monoclinic crystals, space group P21/c; unit
cell parameters at 120(2) K: a = 9.6566(7), b =
6.6457(5), c = 22.676(2) Å; β = 96.632(1)°; V =
1445.5(2) Å3; Z = 4; F(000) = 640; dcalc = 1.407 g/cm3;
µ = 0.099 mm–1; R1 = 0.060 for 2653 independent re-
flections with I > 2σ(I); wR2 = 0.163 for all 3465 inde-
pendent reflections; goodness of fit 1.008. Total of
14040 reflection intensities (Rint = 0.032) were meas-
ured on a Bruker SMART 1K CCD diffractometer
[λ(MoKα) irradiation, graphite monochromator, φ- and
ω-scanning, θmax = 28°]. The structure was solved by
direct methods and was refined in anisotropic approxi-
mation for non-hydrogen atoms. The positions of hy-
drogen atoms were calculated on the basis of geometry
considerations and were refined in isotropic approx-
imation [Uiso(H) = 1.2Ueq(C)]. All calculations were
performed using SHELXTL software package [18].
The complete set of crystallographic data for
compound II was deposited to the Cambridge Crys-
tallographic Data Centre (www.ccdc.cam.ac.uk/
data_request/cif; entry no. CCDC 794281).
3,3′-(1,2-Dihydroxyethane-1,2-diyl)bis(4H-chro-
men-4-one) (III) was synthesized as described above
for compound II in toluene in the absence of HMPA.
Yield 0.0315 g (9%), mp 128–130°C. IR spectrum
(mineral oil), ν, cm–1: 3361 (O–H); 3085 (C–Harom);
2923 (C–H, O–H); 1650 (C=O); 1608, 1573, 1466
1
(C=Carom). H NMR spectrum, δ, ppm: 4.65 s (2H,
OH), 4.67 s (2H, CHOH), 7.45–7.55 m (4H, Harom),
7.71–7.79 m (2H, Harom), 8.01 s (1H, OCH), 8.17 s
(1H, OCH), 8.28–8.31 m (2H, Harom). Mass spectrum:
m/z 175 (Irel 100 %) [M/2]+.
3-Methyl-4H-chromen-4-one (IV) was isolated as
described above for compound II, but the reaction was
carried out in toluene. Yield 0.077 g (22%), mp 62–
1
64°C. H NMR spectrum, δ, ppm: 2.04–2.05 d (1H,
CH3), 7.36–7.44 m (2H, Harom), 7.62–7.67 m (1H,
Harom), 7.80–7.81 d (1H, OCH), 8.23–8.26 q (1H,
H
arom). Mass spectrum, m/z (Irel, %): 160 (100) [M]+,
145 (3) [M – CH3]+, 120 (40) [145 – C2H2]+, 92 (50)
[12 – CO]+, 63 (20) [92 – CO]+.
Compounds V–VII were identified in reaction mix-
tures by mass spectrometry.
4-Oxo-4H-chromene-3-carboxylic acid (VIII)
and 3-hydroxymethyl-4H-chromen-4-one (IX) were
isolated in the reaction carried out as described above
for compound II in the absence of Fe(CO)5.
3-(4-Oxochroman-3-ylmethyl)-4H-chromen-4-
one (II). 4-Oxo-4H-chromene-3-carbaldehyde (I),
0.174 g (1 mmol), was dissolved in 1 ml of benzene,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

TRANSFORMATIONS OF 4-OXO-4H-CHROMENE-3-CARBALDEHYDE
455
nov, N.F., and Tolstikov, G.A., Dokl. Ross. Akad. Nauk,
2009, vol. 429, p. 139.
Compound VIII. Yield 0.01 g (5%), mp 138–
140°C. IR spectrum (mineral oil), ν, cm–1: 3405
(O–H); 3077 (C–Harom); 1665 (C4=O); 1637 (C=O,
7. Terent’ev, A.B., Vasil’eva, T.T., Mysova, N.E., and
Chakhovskaya, O.V., Russ. J. Org. Chem., 2004,
vol. 40, p. 924.
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Mysova, N.E., and Kochetkov, K.K., Russ. J. Org.
Chem., 2007, vol. 43, p. 518.
1
acid); 1614, 1585, 1561 (C=C, C=Carom). H NMR
spectrum, δ, ppm: 6.95–7.00 m (1H, Harom), 7.16–
7.19 d (1H, Harom), 7.59–7.66 m (2H, Harom), 7.87 m
(2H, Harom), 7.87 s (1H, OCH), 12.01 s (1H, COOH).
Compound IX. Yield 0.0088 g (5%), mp 65–67°C.
1H NMR spectrum (300 MHz, CDCl3) δ, ppm: 4.34–
4.36 t (2H, CH2), 5.49 s (1H, OH), 7.53–7.57 m (2H,
Harom), 7.78–7.80 t (1H, Harom), 8.22 s (1H, Harom),
8.34– 8.37 d (1H, Harom).
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hovskaya, O.V., Mysova, N.E., and Hambardzu-
myan, H.H., J. Fluorine Chem., 2008, vol. 129, p. 669.
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This study was performed under financial support
by the Chemistry and Materials Science Department of
the Russian Academy of Sciences (program no. 9,
“Biomolecular and Medicinal Chemistry”) and by the
Russian Foundation for Basic Research (project
no. 09-03-01097).
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