Condensation of ketones in the presence of titanium alkoxides

Article abstract of DOI:10.1023/B:RUJO.0000044535.29531.0d

Titanium alkoxides promote successful condensation of aromatic and aliphatic ketones provided that the liberated alcohol is selectively removed from the reaction mixture.

Full text of DOI:10.1023/B:RUJO.0000044535.29531.0d

Russian Journal of Organic Chemistry, Vol. 40, No. 6, 2004, pp. 763–765. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 6, 2004,
pp. 805–806.
Original Russian Text Copyright © 2004 by Yatluk, Sosnovskikh, Suvorov.
Dedicated to Full Member of the Russian Academy of Sciences
O.N. Chupakhin on his 70th Anniversary
Condensation of Ketones
in the Presence of Titanium Alkoxides
Yu. G. Yatluk, V. Ya. Sosnovskikh, and A. L. Suvorov
Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,
ul. S. Kovalevskoi 20, Yekaterinburg, 620219 Russia
e-mail: eop@ios.uran.ru
Received January 23, 2004
Abstract—Titanium alkoxides promote successful condensation of aromatic and aliphatic ketones provided
that the liberated alcohol is selectively removed from the reaction mixture.
Self-condensation of carbonyl compounds is a well
known process; however, special reagents are
necessary to ensure high yields of the products,
especially from aromatic ketones. Ketones undergo
condensation by the action of polyphosphoric acid, but
in the condensation of acetophenone the yield does not
exceed 27% [1]. Ion-exchange resin can be used
instead of polyphosphoric acid [2]. Some organo-
metallic compounds, e.g., dialkylboron acetates [3],
promote condensation of ketones; in such a way,
(R = Ar) does not change in the series of unbranched
alkoxides (R' = Et, Pr, Bu) and is 38–39%; however,
the yield sharply falls down in going to branched
alkoxides in the series R' = Et, i-Pr, t-Bu (39, 3, and
0%, respectively). Partial replacement of the alkoxy
groups in titanium alkoxide by chlorine also leads to
reduced yield: 39, 28, and 23% for mono-, di-, and tri-
chloro ethoxy derivatives, respectively. In the presence
of water (i.e., with the use of polytitanate) the yield
decreases to 28% (0.5 mol of water per mole of the
alkoxide). The same results are obtained when the
amount of titanium alkoxide is reduced to 0.5, 0.25,
and 0.1 mol/mol: 38, 25, and 7%, respectively. Varia-
tion of the solvent polarity and its boiling point
insignificantly affects the product yield (38, 41, 43,
and 38% for benzene, toluene, xylene, and acetonitrile,
respectively). No reaction occurs in alcohol: the yield
is about 0%. Increase in the reaction time leads to only
slight increase in the yield (38, 48, and 48% in 3, 6,
and 10 h, respectively), and we failed to raise it
appreciably.
1
7
,3-diphenyl-2-buten-1-one (dypnone) was obtained in
2% yield. Aluminum tert-butoxide ensures condensa-
tion of acetophenone in 77–82% yield [4]. Acetone
reacts with titanium alkoxides at room temperature to
afford a titanium derivative of diacetone alcohol, while
on heating, a mixture of di- and triacetone alcohols and
4
-methyl-3-penten-2-one is formed [5]. Numerous
published data on this topic were reviewed in [6].
In the present work we examined the condensation
of aromatic and aliphatic ketones by the action of
titanium alkoxides (Scheme 1).
We have found that the yield of the condensation
product can be increased to a considerable extent when
the liberating alcohol is selectively removed from the
reaction mixture. For this purpose, the reaction was
carried out in a nonpolar solvent (a saturated hydro-
carbon) in a flask equipped with a Dean–Stark trap
which was filled by half with a polar solvent as
extractant (e.g., water, sulfuric or phosphoric acid, or
glycol). A small funnel with a long spout was inserted
into the trap in such a way that the distillate dropped
Scheme 1.
2
RCOCH3
+
Ti(OR')4
2R'OH
RCOCH C(CH )R
3
+
+
TiO(OR')2
To simplify the reaction scheme, the resulting
polytitanate is shown as titanoxane. The reaction
occurs at elevated temperature, and the yield of
the corresponding ketone self-condensation product
1
070-4280/04/4006-0763 © 2004 MAIK “Nauka/Interperiodica”

7
64
YATLUK et al.
Condensation of aromatic ketones ArCOCH
3
in the presence of titanium ethoxide
Ar
Solvent
Heptane
Heptane
Octane
Extractant
95% H SO
Reaction time, min
Yield, %
C
C
C
6
6
6
H
H
H
5
2
4
60
60
45
83
72
87
5
5
5
H
H
2
O
O
2
C
6
H
Isooctane
Heptane
Heptane
Heptane
Heptane
(CH
2
OH)
2
50
60
60
60
50
86
70
60
61
62
4
4
4
2
-CH
3
3
C
6
H
4
85% H
3
PO
4
-CH
OC
6
H
4
H
H
2
2
O
O
6 4
-ClC H
-Thienyl
3 2
HOCH(CH )CH OH
into the funnel and then slowly passed through a layer
of the extractant, where the alcohol was absorbed and
alcohol-free solvent returned into the reaction mixture.
More polar ethanol was absorbed best. Under these
conditions, the reaction time was no longer than 1 h,
and the yields were fairly high. The results are
summarized in table.
corresponding enolate with liberation of ethanol, and
the initial compound can be recovered by acidification.
Scheme 3.
(
CH2)n
(
CH2)n
CCO
Ti(OEt)4
By mixed condensation of acetophenone with
benzaldehyde or benzophenone we obtained chalcone
and α-phenylchalcone in 85 and 2% yield, respec-
tively. Mixed condensation of acetophenone with tri-
fluoroacetophenone in the presence of titanium
ethoxide afforded ethylideneacetophenone and dypnone
as the major products; in addition, α-phenyltrifluoro-
ethanol was detected (the products were identified by
GLC). These data indicate simultaneous occurrence of
the Oppenauer reaction, followed by condensation of
the resulting acetaldehyde with acetophenone and self-
condensation of the latter (Scheme 2).
CCH2
CH CO
2
(
CH )
2 n
Thus the use of titanium ethoxide promotes con-
densation of aromatic and aliphatic ketones in high
yield provided that the liberated alcohol is selectively
removed from the reaction mixture.
EXPERIMENTAL
The purity of products and their composition were
analyzed by GLC using an LKhM-8MD chromatog-
raph equipped with a thermal conductivity detector and
a 2-m×3-mm column packed with 5% of Carbowax on
Chromaton AW-HMDS; carrier gas helium. The prod-
ucts were identified using authentic samples.
Scheme 2.
C H OH
+
CF COPh
3
2
5
Ti(OEt)4
CH CHO
+
CF CH(OH)Ph
3
3
PhCOCH3
+
CH CHO
PhCOCH CHCH3
A mixture of 24 g (0.2 mol) of acetophenone and
3
2
4.08 g (0.1 mol) of ethyl orthotitanate in 30 ml of
We also examined self-condensation of cyclopen-
tanone, cyclohexanone, and cyclooctanone and mixed
condensation of cyclopentanone with cyclohexanone
in the presence of titanium ethoxide (Scheme 3). The
yields of the condensation products were 96, 94, 0, and
heptane was heated under reflux with or without
removal of the liberated alcohol (see above). Sulfuric
acid (d = 1.84), 10 ml, was used to absorb the alcohol.
When the reaction was complete, the mixture was
cooled to room temperature, 20 ml of acetonitrile was
added, and the bottom layer was separated and treated
with 2 ml of hydrochloric acid (d = 1.1). The mixture
was heated to the boiling point and cooled, the solution
8
3%, respectively. In the mixed condensation, the
product ratio cyclopentanone–cyclopentanone:cyclo-
hexanone–cyclopentanone : cyclohexanone–cyclohexa-
none was 22:26:52. It is seen that cyclooctanone fails was separated from the precipitate by decanting, the
to undergo self-condensation; it gives rise to the solvent was distilled off, and the residue was subjected
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004

CONDENSATION OF KETONES IN THE PRESENCE OF TITANIUM ALKOXIDES
765
to fractional distillation under reduced pressure. Yield
of dypnone 18.4 g (83%), bp 138–140°C (1 mm) [7].
3. FRG Patent no. 2417357, 1975; Ref. Zh., Khim., 1976,
no. 18N95.
4
5
6
7
. Danen, C. and Kensler, T.T., J. Am. Chem. Soc., 1940,
vol. 62, p. 3401.
The other reactions were carried out in a similar
way; the products were identified by comparing their
physical constants with those reported in the literature.
. US Patent no. 2799863, 1955; Chem. Abstr., 1955,
vol. 50, p. 4017.
. Neilsen, A.T. and Houlihan, W.J., Org. React., 1968,
vol. 16, p. 1.
REFERENCES
1
2
. US Patent no. 2769842, 1956; Chem. Abstr., 1956,
vol. 52, p. 439.
. Baisted, D.J. and Whitehurst, J.S., J. Chem. Soc., 1961,
. Organic Syntheses, Horning, E.C., Ed., New York:
Wiley, 1955, collect. vol. 3. Translated under the title
Sintezy organicheskikh preparatov, Moscow: Inostran-
naya Literatura, 1952, vol. 3, p. 224.
p. 4089.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004