Synthesis of 4-Formylphenyl 7-Acetyl-8-oxononylcarbamate and europium complex based thereon

Article abstract of DOI:10.1134/S1070428011040051

A new chelating ligand, 4-formylphenyl 7-acetyl-8-oxononylcarbamate, was synthesized starting from 4-hydroxybenzaldehyde and 6-chlorohexyl isocyanate. The reaction of this ligand with europium triisopropoxide gave the corresponding europium(III) complex. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S1070428011040051

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 4, pp. 500–503. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.V. Semenov, N.V. Zolotareva, G.A. Domrachev, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 4,
pp. 503–506.
Synthesis of 4-Formylphenyl 7-Acetyl-8-oxononylcarbamate
and Europium Complex Based Thereon
V. V. Semenov, N. V. Zolotareva, and G. A. Domrachev
Razuvaev Institute of Organometallic Chemistry, Russian Academy of Sciences,
ul. Tropinina 49, Nizhnii Novgorod, 603950 Russia
e-mail: vvsemenov@iomc.ras.ru
Received June 22, 2010
Abstract—A new chelating ligand, 4-formylphenyl 7-acetyl-8-oxononylcarbamate, was synthesized starting
from 4-hydroxybenzaldehyde and 6-chlorohexyl isocyanate. The reaction of this ligand with europium triiso-
propoxide gave the corresponding europium(III) complex.
DOI: 10.1134/S1070428011040051
β-Diketones are universal chelating ligands that are
used in the synthesis of coordination compounds of
non-transition, transition, and rare-earth metals [1–4].
Such ligands endow the corresponding complexes with
such properties as volatility, solubility, and resistance
to oxygen and moisture. Modern technologies imply
the necessity of synthesizing complexes with function-
alized organic ligands to ensure their application in
heterogeneous catalysis, medicine, and optics.
frequently than complexes of other metals due to
photoluminescence in the red (Eu3+) or green (Tb3+)
region of the spectrum. The problem related to chem-
ical binding of a biomarker to proteins is solved by
introduction of an organic group capable of reacting
with fragments of polypeptide chain. The choice of
appropriate groups is strongly limited. A few known
examples include isothiocyanate [8] and sulfonyl
chloride derivatives [9]. A complex having a primary
amino group in the ligand can be linked to protein
through glutaraldehyde which readily reacts with
amino groups in both protein and the complex [10].
Coordination compounds of rare-earth metals are
used as luminescent labels in medical diagnostics
[5–7]. Europium and terbium complexes are used more
Scheme 1.
H
CHO
N
O
Et3N
Cl
NCO
+
Cl
O
HO
CHO
I
II
III
O
H
(1) NaI, Me2CO
(2) MeC(O)CH2C(O)Me, K2CO3, Me2CO
N
O
Me
O
Me
O
CHO
IV
Me
H
O
N
Eu(OPr-i)3
O
O
Eu
OHC
Me
O
3
n
V
500

SYNTHESIS OF 4-FORMYLPHENYL 7-ACETYL-8-OXONONYLCARBAMATE
501
An aldehyde group present in the ligand molecule
should ensure direct binding of luminescent label to
biomolecule. In the present work we tried to imple-
ment the above approach with the use of acetylacetone
as most popular and accessible representative of pen-
tane-2,4-diones [11].
tion at 1465, 1385, and 730 cm–1. A strong band at
1212 cm–1 corresponds to C–O–C stretching vibrations
of the ester group. Compound II displayed in the
1H NMR spectrum two triplets, two quintets, and one
multiplet with an intensity ratio of 1:1:1:1:2. Two
downfield triplets at δ 3.53 and 3.30 ppm belong to
protons in the terminal CH2 groups which are linked to
electronegative substituents (Cl, σI = 0.43; NCO, σI =
0.38) [13]; the neighboring methylene protons resonat-
ed as two quintets at δ 1.74 and 1.62 ppm, and the
multiplet signal at δ 1.36–1.49 ppm corresponds to two
central methylene units in the six-membered chain.
Addition of 4-hydroxybenzaldehyde slightly affects
the position of the above signals, but four downfield
signals appear due to protons in the NH (δ 7.00 ppm),
p-phenylene (δ 7.32–7.36, 7.91–7.95 ppm), and alde-
hyde groups (δ 9.99 ppm).
As starting compounds for functionalization of
acetylacetone we selected 4-hydroxybenzaldehyde (I)
and 6-chlorohexyl isocyanate (II). Compound I was
the source of aldehyde group, and isocyanate II was
used as spacer providing the possibility for introduc-
tion of an aldehyde group into β-diketone molecule. It
is known [12] that alcohols and phenols readily react
with isocyanates to give carbamic acid esters
(urethanes). Organic substituent can be introduced into
the methylene group of β-diketone via reaction of
halogen derivatives with CH acid in the presence of
hydrogen halide acceptor, e.g., primary amine or alkali
metal carbonate. The reaction sequence leading to the
target ligand, 4-formylphenyl 7-acetyl-8-oxononylcar-
bamate (IV), is shown in Scheme 1. 4-Hydroxybenz-
aldehyde (I) reacted with 6-chlorohexyl isocyanate to
give 4-formylphenyl 6-chlorohexylcarbamate (III).
Taking into account that nucleophilic substitution in
iodoalkanes occurs more readily than in chloro ana-
logs, compound III was initially converted into iodo
derivative. The subsequent reaction with acetylacetone
was carried out in the presence of potassium carbonate
which ensured better results as compared to triethyl-
amine.
Comparison of the IR spectra of III and IV (see
figure) shows complication of the spectral pattern in
the range from 1700 to 1500 cm–1 in going from III to
IV, which may be due to the presence of two carbonyl
groups in the acetylacetone fragment. The spectral
pattern in the regions 3500–2700 and 1500–500 cm–1
1
changes less significantly. The H NMR spectrum of
IV contained two singlets from methyl protons in the
1
2
3
Compound III was isolated as a white powder, and
compound IV was a colored viscous liquid. Our at-
tempts to purify these compounds by vacuum sublima-
tion were unsuccessful: decomposition occurred with
formation of non-volatile tarry products. The progress
of the reaction of aldehyde I with isocyanate II can be
readily monitored by IR spectroscopy, following dis-
appearance of the characteristic NCO absorption band
at 2271 cm–1. Figure shows the IR spectra of isocy-
anate II and addition product III. The IR spectrum of
the latter contained absorption bands due to stretching
vibrations of the amide N–H group at 3337 cm–1,
aromatic C–H bonds at 3065 cm–1, and aldehyde C–H
bond at 2738 cm–1. A number of strong absorption
bands in the region 1800–1500 cm–1 were assigned to
vibrations of the carbamate and aldehyde fragments
[1740 (C=O, aldehyde), 1698 (amide I), 1531 cm–1
(amide II)], as well as of aromatic C=C bonds (1600,
1498 cm–1). The presence of a hydrocarbon chain con-
sisting of six methylene units is confirmed by absorp-
4000
3000
2000
1000 ν, cm–1
IR spectra of (1) 6-chlorohexyl isocyanate (II), (2) 4-formyl-
phenyl 6-chlorohexylcarbamate (III), and (3) 4-formyl-
phenyl 7-acetyl-8-oxononylcarbamate (IV).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 4 2011

SEMENOV et al.
502
β-diketone fragment at δ 2.12 (ketone) and 2.21 ppm
(enol), a signal from the CH proton at δ 5.46 ppm (di-
ketone tautomer), and a signal from the enolic hydroxy
proton at δ 15.30 ppm.
dissolved in 50 ml of tetrahydrofuran, 27.62 g
(171 mmol) of 6-chlorohexyl isocyanate (II) and
0.10 g (1 mmol) of triethylamine were added, the mix-
ture was heated for 20 h at 90°C, and the solvent was
distilled off under reduced pressure. The residue was
a viscous liquid which was washed first with toluene
and then with hexane. The solvent was removed under
reduced pressure. Yield 25.03 g (77%), white powder,
mp 43°C. IR spectrum, ν, cm–1: 3336 (N–H); 3063
(C–Harom); 2936, 2859 (C–Haliph); 2735 (C–Hald); 1737
(C=O, aldehyde); 1697 (C=O, amide I); 1598
Functionalized β-diketon (IV) rapidly reacted with
europium triisopropoxide in THF to give insoluble
β-diketonate V. Poor solubility of the product suggests
that the complex exists as coordination polymer. Anal-
ogous pattern was observed for anhydrous tris(acetyl-
acetonato)europium(III) [14]. We succeeded in con-
verting compound V into a soluble state only by
heating with excess tributylphosphine oxide (but not
with phenanhtroline) in acetone. A solution of V in
Bu3P=O showed a very weak cationic luminescence
which considerably increased upon addition of an equi-
molar amount of phenanthroline. The photolumines-
cence spectrum contained four emission bands due to
europium cation with their maxima at 537 (5D1 → 7F1),
557 (5D1 → 7F2), 594 (5D0 → 7F1), and 616 nm (5D0 →
7F2), the latter being the most intense. Fluorescence
of the ligand was observed as a broad band centered
at λ 475 nm.
1
(C=Carom); 1534 (δNH, amide II). H NMR spectrum
(acetone-d6), δ, ppm: 1.41–1.49 m (4H, CH2CH2),
1.53–1.65 m (2H, CH2CH2NH), 1.72–1.82 m (2H,
CH2CH2Cl), 3.18–3.28 q (2H, CH2NH, J = 6.3 Hz),
3.57–3.64 t (2H, CH2Cl, J = 6.8 Hz), 7.00 s (1H, NH),
7.32–7.36 d (2H, 3′-H, 5′-H, J = 8.5 Hz), 7.91–7.95 d
(2H, 2′-H, 6′-H, J = 8.53 Hz), 9.99 s (1H, CHO).
Found, %: C 59.16; H 6.33; Cl 12.00. C14H18ClNO3.
Calculated, %: C 59.26; H 6.35; Cl 12.52.
4-Formylphenyl 7-acetyl-8-oxononylcarbamate
(IV). A solution of 23.25 g (82 mmol) of compound
III in 30 ml of acetone was added to a solution of
13.70 g (91 mmol) of sodium iodide in 80 ml of
acetone. The mixture was stirred for 6 h at 80°C, the
precipitate of sodium chloride was filtered off, and
8.00 g (0.80 mmol) of acetylacetone and 12.30 g
(89 mmol) of potassium carbonate were added. The
mixture was stirred for 7 h at 80°C and filtered, and
the solvent and volatile products were distilled off
from the filtrate under reduced pressure at 50°C. Yield
16.60 g (59%), viscous yellow–green liquid. IR spec-
trum, ν, cm–1: 3333 (N–H); 3086 (C–Harom); 2936,
2863 (C–Haliph); 2743 (C–Hald); 1724 (C=O); 1687
(C=O, amide I); 1647, 1601, 1577, 1510 (δNH, amide
Thus we have demonstrated the possibility for syn-
thesizing luminescent europium(III) coordination com-
pound in which the ligand possesses an aldehyde group
capable of reacting with polypeptide chain.
EXPERIMENTAL
The IR spectra were recorded from films between
KBr plates or dispersions in mineral oil on an FSM
1201 spectrometer with Fourier transform. The
1H NMR spectra were obtained on a Bruker Avance
DPX-200 instrument (200 MHz) at 25°C using tetra-
methylsilane as internal reference. The fluorescence
and fluorescence excitation spectra of compound V
were measured on a Perkin–Elmer LS-55 spectro-
fluorimeter from a solution in Bu3P=O–acetone (1:5
by volume) in the presence of an equimolar amount of
phenanthroline. 4-Hydroxybenzaldehyde, 6-chloro-
hexyl isocyanate, and acetylacetone were analyzed on
a Tsvet-800 gas chromatograph equipped with a ther-
mal conductivity detector and a 0.3×300-cm column
packed with 5% of SE-30 on Inerton-AW; carrier gas
helium. Europium triisopropoxide was synthesized
from anhydrous EuCl3 and NaOPr-i according to the
procedure described in [15]. 4-Hydroxybenzaldehyde
was sublimed under reduced pressure, and acetyl-
acetone was distilled prior to use.
1
II). H NMR spectrum (acetone-d6), δ, ppm: 1.06–
1.13 m (4H, CH2CH2), 1.27–1.58 m (2H, CH2CH2NH),
1.68–1.87 m (2H, CH2CH2CH), 2.12 s and 2.21 s (3H
each, CH3), 3.15–3.25 m (2H, CH2NH), 3.34–3.44 m
(2H, CH2CH), 5.46 s (1H, CH), 6.98–7.02 d (2H, 3′-H,
5′-H, J = 8.5 Hz), 7.36 s (1H, NH), 7.76–7.80 d (2H,
2′-H, 6′-H, J = 8.5 Hz), 9.83 s (1H, CHO), 15.30 s
(1H, OH, enol). Found, %: C 64.56; H 7.03; N 3.87.
C19H25NO5. Calculated, %: C 65.67; H 7.26; N 4.03.
Tris(4-formylphenyl 7-acetyl-8-oxononylcarba-
mato)europium(III) (V). An ampule was charged
with a solution of 2.65 g (8 mmol) of compound IV in
5 ml of THF, a solution of 0.84 g (2.5 mmol) of
Eu(OPr-i)3 in 5 ml of THF was added, and the ampule
was evacuated, sealed, and heated for 3 h at 80°C.
After cooling, the ampule was opened, and the precip-
4-Formylphenyl 6-chlorohexylcarbamate (III).
4-Hydroxybenzaldehyde (I), 13.92 g (114 mmol), was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 4 2011

SYNTHESIS OF 4-FORMYLPHENYL 7-ACETYL-8-OXONONYLCARBAMATE
503
3. Kuz’mina, N.P., Mironov, A.V., and Rogachev, A.Yu.,
itate was separated by centrifugation, washed with
THF, toluene, and diethyl ether, and dried under
reduced pressure. Yield 1.50 g (47%), yellow powder
insoluble in THF, toluene, diethyl ether, methylene
chloride, and acetonitrile and soluble in tributylphos-
phine oxide. IR spectrum, ν, cm–1: 3333, 1015, 917,
836, 765, 650. Luminescence spectrum (λexcit 340 nm),
Ros. Khim. Zh., 2004, vol. 48, p. 15.
4. Vigato, P.A., Peruzzo, V., and Tamburini, S., Coord.
Chem. Rev., 2009, vol. 253, p. 1099.
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6. Eliseeva, S.V. and Bunzli, J.-C.G., Chem. Soc. Rev.,
5
7
2010, vol. 39, p. 189.
λ, nm: 475 (ligand), 537 (Eu D1 → F1), 557 (Eu
7
5
7
5
7
5D1 → F2), 594 (Eu D0 → F1), 616 (Eu D0 → F2).
Found, %: C 56.86; H 6.73; Eu 12.31. C57H75N3O15Eu.
Calculated, %: C 57.33; H 6.33; Eu 12.73.
7. Bunzli, J.-C.G., Chem. Rev., 2010, vol. 110, p. 2729.
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This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 08-03-00771, 10-03-90006Bel), by the Ministry
of Education and Science of the Russian Federation
(project no. GK 16.740.11.0015), and by the Presidium
of the Russian Academy of Sciences (program “Target-
Oriented Synthesis of Substances with Specified Prop-
erties and Design of Functional Materials Based
Thereon”).
10. Yuan, J., Wang, G., Kimura, H., and Matsumoto, K.,
Anal. Biochem., 1997, vol. 254, p. 283.
11. Peshkova, V.M. and Mel’chakova, N.V., β-Diketony
(β-Diketones), Moscow: Nauka, 1986.
12. Saunders, J.H. and Frisch, K.C., Polyurethanes: Chem-
istry and Technology, New York: Intersci., 1962–1964.
13. Vereshchagin, A.N., Induktivnyi effekt. Konstanty za-
mestitelei dlya korrelyatsionnogo analiza (Inductive
Effect. Substituent Constants for Correlation Analysis),
Moscow: Nauka, 1988.
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