Increased conversion to 2,4,6-triarylpyrylium salt: Aldol cyclotrimerization of acetophenone in BMImPF6 ionic liquid

Article abstract of DOI:10.1002/jccs.200800075

Substituted acetophenone 1 in BMImPF₆ ionic liquid, heated at 120 °C for 24 h, produces β-methylchalcone 2, triarylbenzene 3, and triarylpyrylium salt 4. BMImPF₆ catalyzes the self-aldol condensation of 1, whose cyclotrimerization gi

Full text of DOI:10.1002/jccs.200800075

5
12
Journal of the Chinese Chemical Society, 2008, 55, 512-516
Communication
Increased Conversion to 2,4,6-Triarylpyrylium Salt: Aldol
Cyclotrimerization of Acetophenone in BMImPF Ionic Liquid
6
a,b
a,c
a,c
) and Ling-Kang Liu * (
Po-Neng Chuang
a
(
), Tsao-Dong Wu
(
Institute of Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan, R.O.C.
)
b
Department of Chemistry, National Central University, Jhongli, Taoyuan 32001, Taiwan, R.O.C.
c
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan, R.O.C.
Substituted acetophenone 1 in BMImPF
chalcone 2, triarylbenzene 3, and triarylpyrylium salt 4. BMImPF
6
ionic liquid, heated at 120 °C for 24 h, produces b-methyl-
catalyzes the self-aldol condensation
6
of 1, whose cyclotrimerization gives an increased conversion to 4 at the expense of 3 normally obtained
from the cyclotrimerization of 1 in common organic solvent.
Keywords: Ionic liquid; Acetophenone; Self-aldol condensation.
Room temperature ionic liquids (RTILs), a class of
organic salts that melt below 100 °C, are often used as sol-
vent in homogeneous catalysis in order to take advantages
of negligible vapor pressure, high thermal stability, tunable
Scheme I Friedel-Crafts acetylation reaction of naph-
thalene
O
1
polarity, etc. The highly polar nature of RTILs likely in-
O
Cl
O
Cl
EMImAl Cl
7
O
C H NO
6
5
2
2
creases the life time of a charge-separated transition state
2
-isomer
1-isomer
during reaction. Seddon et al. found that, employing
2 7
EMImAl Cl melts in the Friedel-Crafts acetylation reac-
tion of naphthalene, the thermodynamically unfavored 1-
isomer became the major product whereas the thermody-
Scheme II Pd-catalyzed Heck arylation reaction of
olefin and aryl halide
namically favored 2-isomer exhibited only a 2% yield
2
Scheme I). Xiao et al. also reported that the Pd-catalyzed
R
R
(
[Pd], base
DMF
[Pd], base
BMImBF4
R
Heck arylation reaction of electron rich olefins and aryl
halides in BMImBF produced essentially the less common
X
linear product
branched product
4
3
branched products, not the linear ones (Scheme II). These
results suggested that as media of reactions, RTILs could
shift the reaction to follow the more ionic pathways.
Conventionally aldol condensation reactions were
In this report we wish to present the observation of
aldol cyclotrimerization of acetophenone mediated by
BMImPF
6
, without the addition of base. The cyclotrimeri-
4
zation was found to produce in substantial amounts the
performed in organic solvents. In 2002, Mehnert et al.
9
,4,6-triarylpyrylium salts in addition to the more familiar
2
1
started investigation of the aldol condensation reactions
employing imidazolium ionic liquid phases treated with
,3,5-triarylbenzene. That is in sharp contrast to the results
5
aqueous solution of NaOH as the catalyst. Later, piperi-
of conventional preparation of 1,3,5-triarylbenzene in or-
ganic phase with Lewis acid catalyzed aldol cycloconden-
6
7
dine and L-proline in RTIL, respectively, were studied
4
,10-12
extensively. Also appeared were the pyrrolidine-function-
8
alized ionic liquids for the aldol condensation reactions.
sation.
Herein substituted acetophenone 1 and hydrophobic
BMImPF ionic liquid were mixed well in a round bot-
tomed flask equipped with a condenser and the solution
Up to the present time, the base catalyzed aldol condensa-
tion reactions in ionic liquids have been documented.
6
*
Corresponding author. Fax: +886-2-27831237; E-mail: liuu@chem.sinica.edu.tw

Increased Conversion to 2,4,6-Triarylpyrylium Salt
J. Chin. Chem. Soc., Vol. 55, No. 3, 2008 513
6 4 2
C H Cl , 180 °C for 24 h; no 2,4,6-triarylpyrylium forma-
stirred and maintained constantly at 120 °C. During the re-
action the mixture became increasingly viscous, even so-
lidified. After 24 h, the reaction was stopped and the reac-
1
tion being indicated. Obviously the aldol cyclotrimeriza-
2
tion reaction of 1 in organic solvents produces mainly 3;
tion mixture extracted with Et
Et O fractions were rotary evaporated and the crude puri-
fied with SiO column chromatography. In addition to un-
2
O for 3 times. The combined
similar reaction in hydrophobic BMImPF
stantially the ionic 4, in addition to the neutral 3.
Though formulated as the PF salt, the anions of 4a-c
6
produces sub-
2
2
6
-
31
used acetophenone, b-methylchalcone 2 and triarylben-
zene 3 were obtained (Scheme III, with conversions).
were not 100% PF
6
, nonetheless. In the P NMR spectra,
1
4a-c exhibited a septuplet at ca d -145 with JPF = 711 Hz
-
Without BMImPF
6
ionic liquid, only acetophenone was re-
(assigned to PF
6
) plus a singlet at ca d -1.8 (assigned to
covered after being heated at 120 °C for 24 h. With hydro-
H
3
PO ) with intensities varying from sample to sample. In
4
1
the F NMR spectra, 4a-c exhibited a doublet at ca d -70
9
philic BMImBr ionic liquid, there was no reaction either.
1
-
with JPF = 711 Hz (assigned to PF
-147 (assigned to HF) with varying intensity, too. These
NMR data suggested existence of the H O-HF-P phase
are likely equilibrated by hy-
6
) and a singlet at ca d
Scheme III Aldol condensation reaction of aceto-
phenone in BMImPF6
2 5
O
2
-
6 3 4
system in that PF and H PO
1
drolysis, leading to the existence of fluorides in the
3
Ar
Ar
O
BMImPF6
Ar
Ar
O
o
20 C, 24 h
system.
1
O
6
Hydrophobic BMImPF ionic liquid was regarded as
Ar
Ar
Ar Ar
Ar
thermally stable with a thermal decomposition temperature
14
at 349 °C as shown in TGA studies. However, Kosmulski
PF6
1
a
b
c
2
3
4
4/3
0.1
0.1
0.6
C H
52%
37%
12%
33%
43%
36%
2%
4%
21%
6
p-MeC H4
5
et al. reported that wet spots could be observed in crucibles
6
p-MeOC H4
of TGA after conditioning bmimPF
6
at 200 °C for 10 h, i.e.
6
the thermal decomposition temperature based on fast TGA
1
scans does not imply a long term thermal stability. In our
5
The reaction mixture after Et
2
O extraction was then
added with just enough amounts of EtOH in order to keep
the ionic liquid in solution. After standing for 24 h, triaryl-
experiments, the ionic liquid layer after the reaction was
1
also examined with H NMR, whose spectrum revealed
pyrylium PF
6
salt 4 precipitated and the salt was character-
two different sets of BMIm peaks. One set of signals was
1
ized by NMR ( H, C, F, and P) and other analytical
1
methods. In the H NMR spectra of 4b, for example, the
13
19
31
identical to that of BMImPF ; the other set associated with
6
-
-
6 6 6
anion(s) other than PF . The PF anions of the BMImPF
singlet resonance at d 9.06 was assigned to the pyrylium
ring protons, downfield shifted by 1.3 d units when com-
pared to the singlet resonance at d 7.73 assigned to the in-
ner benzene ring protons of 3b, attributable to the highly
electron-withdrawing nature of cationic pyrylium.
ionic liquid at 120 °C in the long term presence of 1 must
have degraded to produce at least tracing fluorides and PF5
to catalyze the aldol condensation of 1.
-
The PF anion has been known to be weakly coordi-
6
1
6
nating. Gilbert et al. reported that in ionic liquids with
+
3
Because in the above experiments, 2 is a dimeric in-
termediate of 1 and both 3 and 4 are trimers of 1, it is inter-
esting to look into more details the ratios of conversion on
weakly coordinating anions, tracing water exists as H O ,
1
7
not H O . Under the constraint, the ionic liquids would al-
2
2
6
2
low aldol addition followed by slow H O elimination. Loh
4
a/3a, 4b/3b, and 4c/3c, at ca 0.1, 0.1, and 0.6, respec-
et al. observed that L-proline in BMImPF catalyzes aldol
tively. A more electron releasing substituent at 1 favors the
production of 4.
reactions in that H O elimination products could not be ob-
7(b)
served within 20 h. In line with the slower H O elimina-
2
Jing et al. detailed the treatment of 1 with p-tolylsul-
tion steps, a mechanism is proposed in Scheme IV for the
fonyl acid and a catalytic amount of SnCl
4
in C
5
H
1
11OH to
production of 4 in BMImPF ionic liquid. Adepronated and
6
1
produce 3 in good yields without noticing 4. Alterna-
tively the strategy of Lewis acid promoted cyclotrimeri-
zation of acetyl aromatics lead to 1,3,5-triarylbenze forma-
activated 1 adds to a second molecule of 1 to form the inter-
mediate structure A, which after elimination of H O equiv-
2
alent, results in 2. When 2 is depronated and activated, it
tion (100% yield) with conditions of TiCl
4
(1.5 eq), o-
adds to a third molecule of 1 to form intermediate structure

5
14 J. Chin. Chem. Soc., Vol. 55, No. 3, 2008
Chuang et al.
Scheme IV Proposed mechanism for aldol cyclotri-
Scheme V Aldol condensation reaction of acetophen-
merization of acetophenone derivatives in
one derivatives upon dissolution of NaPF6
BMImPF
6
Ar
NaPF6
Ar
O
Ar
Ar
O
Ar
o
20 C, 24 h
1
O
1
F
O
O
H
Ar
O
F4P
F
H
PF5
Ar
Ar
Ar
Ar Ar
Ar
PF6
Ar
Ar
O
1
O
A
1
a
b
c
2
3
4
4/3
0.5
0.7
1.8
PF5
Ar
PF5
C H
40%
3%
20%
35%
44%
18%
17%
30%
32%
6
p-MeC H4
5
PF5
Ar
6
O
p-MeOC H4
Ar
O
F
Ar
6
Ar
H
Ar
O
1
PF5
A
1b/NaPF
heated at 120 °C for 24 h. In this case the 4/3 ratio was
found to be 1.6, higher than 0.1 with only BMImPF and
0.7 with only NaPF
As a conclusion, the BMImPF
aldol cyclotrimerization of acetophenones 1 are PF
lyzed processes with a slow H O elimination step; the
cyclotrimerization of 1 in BMImPF ionic liquid and the
cyclotrimerization of 1 upon reactive dissolution of NaPF
6 6
/BMImPF (10 mmol/10 mmol/2 mL) was also
Ar
O
Ar
2
Ar
O
O
H
PF5
PF5
PF5
PF5
6
Ar
Ar
O
F
6
.
Ar
PF4
O
6
ionic liquid mediated
cata-
O
Ar
H
PF4
Ar
O
O
Ar
F
Ar
5
B
PF5
D
2
6
Ar
Ar
Ar
O
H
6
in 1 exhibit noted conversion to the trimeric product of
2,4,6-triarylpyrylium salts 4 at the expense of 1,3,5-triaryl-
benzenes 3.
Ar
Ar
Ar
Ar
Ar
Ar
O
O
3
Ar
C
Ar
O
PF4
F
E
Ar
Ar
4
EXPERIMENTAL SECTION
General procedures
B. Similar elimination gives C whose dehydration yields
the cyclotrimeric product 3. Alternatively, if the deproton-
ated and activated 2 adds to structure A (accumulated be-
cause of the slower elimination step); the outcome changes
to intermediate structures D then E, in that the formation of
a remote double bond is followed by its extrusion via the
Into a single-neck round-bottomed flask (50 mL) was
introduced a stirring bar, substituted acetophenone (50
6
mmol) and bmimPF (10 mL, 58 mmol), then fitted with a
condenser, before the temperature of the mixture being
raised and kept at 120 °C for 24 h with constant stirring. Af-
ter this, the mixture was cooled down to room temperature
1
8
6
-membered cyclic transition state to yield the cyclotri-
meric product 4. The polymeric materials found in these re-
actions is consistent to the extrusion of ArCMe=CH
As the imidazolium cations were spectators only, the
same chemistry also worked with other dissolving PF
salts. The NaPF dissolution in 1 was similarly investigated
and quenched by extraction with Et
combined Et O fractions were rotary evaporated. The crude
was purified by SiO column chromatography, eluting with
:10 Et O/hexanes, to recover 1, yield oily 2 and solid 3.
2
O (3 ´ 15 mL). The
2
2
.
2
1
2
6
Compound 2 slowly solidified upon standing at room tem-
perature. Compound 3 was recrystallized from CH Cl /
6
2
2
at 120 °C for 24 h in that the aldol cyclotrimerization reac-
EtOH. The remaining ionic liquid layer was added with just
enough amounts of EtOH and let stand for 24 h to give pre-
cipitate 4. Conversions are shown in Scheme III. Similarly,
tion also proceeded. The conversion results after the same
Et
2
O and EtOH workup were given in Scheme V. Noted
were the increasing conversions of both 3 and 4 in the
6
acetophenone reaction with NaPF (10 mmol each) was
NaPF
NaPF
6
studies, presumably the reactive dissolution of
carried out with conversions shown in Scheme V.
in 1 gave high ion concentrations in the mixture and
Characterization data
1
2a yellow solid (CAS 495-45-4), mp 56 °C; H NMR
6
the conversion was seemingly faster than in BMImPF
6
. To
avoid solidification of mixtures in flask, a combination of
(CDCl ): d 7.8-7.5 (m, 10H), 7.2 (s, 1H), 2.6 (s, 3H); MS-
3

Increased Conversion to 2,4,6-Triarylpyrylium Salt
J. Chin. Chem. Soc., Vol. 55, No. 3, 2008 515
1
0(b)
EI: m/z 222.
3a white solids (CAS 612-71-5), mp
68-169 °C; H NMR (CDCl ): d 7.77 (s, 3H), 7.68-7.70
m, 6H), 7.45-7.49 (m, 6H), 7.36-7.39 (m, 3H); MS-EI: m/z
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3
(
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06. 4a fluorescing yellow powder, H NMR (d -DMSO):
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3
2
2
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d 9.17 (s, 2H), 8.59-8.61 (m, 6H), 7.86-7.89 (m, 3H), 7.77-
1
.82 (m, 6H); C NMR (d -DMSO): d 170.09, 165.13,
3
6
7
1
1
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35.13, 134.99, 132.49, 130.00, 129.83, 129.80, 129.11,
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9
6
28.78, 115.20; F NMR (d -DMSO): d -69.5 (d, J = 711
2
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Commun. 1998, 2097-2098.
3
1
Hz); P NMR (d -DMSO): d -144.9 (septet, J = 711 Hz);
6
+
MS-EI: m/z 309 ([M – A] ).
20
3. Mo, J.; Xu, L.; Xiao, J. J. Amer. Chem. Soc. 2005, 127, 751-
760.
1
b yellow solid (CAS 36201-04-4), mp 57-58 °C; H
2
NMR (CDCl
3
): d 7.92 (d, 2H), 7.49 (d, 2H), 7.26 (d, 2H),
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.22 (d, 2H), 7.17 (s, 1H), 2.61 (s, 3H), 2.41 (s, 3H), 2.39
1
0(b)
(
s, 3H); MS-EI: m/z 250.
3b white solids (CAS 50446-
3-0), mp 167-168 °C; H NMR (CDCl ): d 7.73 (s, 3H),
.59 (d, J = 8 Hz, 6H), 7.27 (d, J = 8 Hz, 6H), 2.41 (s, 9H);
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4
7
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9(c)
1
4b fluorescing yellow powder, H
MS-EI: m/z 348.
6
NMR (d -Acetone): d 9.06 (s, 2H), 8.46-8.54 (m, 6H), 7.60-
1
.65 (m, 6H), 2.53-2.54 (m, 9H); C NMR (d -DMSO): d
3
6
7
1
1
69.15, 163.79, 146.80, 146.16, 130.43, 129.94, 129.34,
1
28.48, 126.20, 113.03, 21.40, 21.36; F NMR (d -
3
DMSO): d -72.8 (d, J = 711 Hz), -147.6; P NMR (d -
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6
1
6
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+
51 ([M – A] ). 2c yellow solid (CAS 16197-83-4), mp
21
3
8
3
1
4-85 °C; H NMR (CDCl
3
): d 7.9-7.8 (m, 8H), 7.1 (s, 1H),
1
0(b)
.8 (s, 6H), 2.5 (s, 3H); MS-EI: m/z 282.
3c white solids
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.65 (s, 3H), 7.62 (d, 6H, J = 9.3 Hz), 7.02 (d, 6H, J = 9.3
1
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7
9
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9(c)
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1
ange crystals, H NMR (d -DMSO): d 8.82 (s, 2H). 8.61-
4c fluorescing or-
6
8
3
1
1
7
7
.64 (d, 2H), 8.50-8.53 (d, 4H), 7.29-7.32 (m, 6H), 3.96-
1
.98 (m, 9H); C NMR (d -DMSO): d 167.37, 165.21,
3
6
1
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10.25, 55.97, 55.83; F NMR (d -DMSO): d -70.2 (d, J =
9
6
3
11 Hz), -147.6; P NMR (d -DMSO): d -144.9 (septet, J =
1
6
+
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1
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