LETTER
1947
Triple Self-Condensation of Ketones Yielding Aromatics Promoted with
Titanium Tetrachloride
T
riple Self-Con
i
densati
l
on of
K
o
e
tones ng Li,a Wen-Hua Sun,*a Xianglin Jin,b Changxing Shaoa
a
State Key Laboratory of Engineering Plastics and The Center for Molecular Sciences, Institute of Chemistry, The Chinese Academy of
Sciences, Beijing 100080, China
b
Institute of Physical Chemistry, Peking University, Beijing 100871, China
Fax +86(10)62566383; E-mail: whsun@infoc3.icas.ac.cn
Received 20 September 2001
heated and refluxed for 24 hours. The resulting black so-
lution was poured into ice water (30 mL). The product
was extracted with ether (3 20 mL) and washed with wa-
ter and brine, then dried over MgSO4. After the solvent
was evaporated, column chromatography (silica gel, pe-
troleum ether/ether = 10:1) gave 1,3,5-tri(4-chlorophe-
nyl)benzene (1.03 mmol, 0.4213 g). The isolated yield
was 77%. However, when one equivalent of TiCl4 (10
mmol, 1.1 mL) with the ketone (10 mmol, 1.5459 g) in
toluene (40 mL) was refluxed for 24 hours, the 1,3,5-tri(4-
chlorophenyl)benzene was isolated in 67% yield (2.22
mmol, 0.9113 g). It was observed for other ketones that
two equivalents of TiCl4 were necessary to undergo the
triple self-condensation for forming their corresponding
products in reasonable yields, but very low yields (or even
a trace of expected product) were observed in their equiv-
alent reactions. As in the case of SiCl4 promoted triple
self-condensation,4 the cyclohexanone was treated with
TiCl4 to isolate the triannulated benzene, and the corre-
sponding product of cyclopentanone. All the products ob-
tained were characterized by NMR and elemental analysis
techniques. The crystal structure of the new compound
1,3,5-tri(2-naphthyl)benzene7 was determined by single
crystal X-ray diffraction (Figure 1).
Abstract: Triple self-condensation of ketones was promoted by ti-
tanium tetrachloride in toluene to afford corresponding benzene de-
rivatives, and the structure of tri(2-naphthyl)benzene was
confirmed by X-ray single crystal diffraction.
Key words: ketones, self-condensation, titanium tetrachloride,
substituted benzene, enolate
Besides being used as catalysts in polyolefins,1 TiCl4 has
attracted great attention in organic synthesis. For instance,
it was used to promote self-condensation of acetophe-
nones with the assistance of TiCl4 in pyridine.2 Recently
carbon-rich compounds, such as conjugated polyaromat-
ics and dendrimers, are finding many interests because of
their superior electronic, magnetic or catalytic properties.
Silicon tetrachloride was used to promote the triple con-
densation of aryl methyl ketones to yield 1,3,5-triarylben-
zenes.3,4 So far, there is no report on the use of TiCl4 for
triple condensation of ketones. Recently we found that the
treatment of ketones with TiCl4 could allow the triple con-
densation for forming the corresponding benzene deriva-
tives (Scheme 1). As shown in the SiCl4-promoted triple
self-condensation reactions, ketones should be aryl meth-
yl ketones and cycloalkanones. Beyond this limitation, a
hexa-substituted benzene was also formed through con-
densation of propiophenone in our case.
In addition, the reaction of propiophenone with TiCl4 was
also examined (Scheme 2). The new product,8 1,3,5-triph-
enyl-2,4,6-trimethylbenzene, was formed in the first time
by the use of this method in 32% isolated yield.
R
R'
R'
R
TiCl4
O
In the case of SiCl4 promoted self-condensation of ke-
tones, it is necessary to use excess amount of chloride3,4 to
obtain high yield. In the present work a similar condition
was also found to be essential to get higher yield. Howev-
er, the stoichiometric reaction of 4-chloroacetophenone
with TiCl4 gave 67% isolated yield of its corresponding
product, comparing 77% isolated yield in the reaction
with two equivalents of TiCl4. According to this result, it
was believed that stoichiometric amount of TiCl4 is theo-
retically necessary for the reaction. Therefore the reaction
mechanism is proposed in Scheme 3. TiCl4 is recognized
as a strong Lewis acid with high affinity for oxygenated
organic molecules as well as having powerful dehydrating
ability. TiCl4 reacts with ketone to form ketone–TiCl4 ad-
dict.2,6 Such addicts could subsequently transfer into cat-
ion-anion pair in betaine form or chlorotitanium-enolate5
which can be equilibrated to -keto carbanion. Nucleo-
R'
R
R
R'
Scheme 1
The triple self-condensation of a ketone was carried out
by refluxing the ketone mixture with two equivalents of
TiCl4 in toluene. Results are presented in the Table. In a
typical example, two equivalents of TiCl4 (8 mmol, 0.88
mL) are added dropwise at 0 °C to a solution of 4-chloro-
acetophenone (4 mmol, 0.6184 g) in toluene (15 mL). Af-
ter stirring for several minutes, the reaction mixture was
Synlett 2001, No. 12, 30 11 2001. Article Identifier:
1437-2096,E;2001,0,12,1947,1949,ftx,en;Y17001ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214