BTISA-catalyzed Friedel-Crafts bimolecular cyclization of cinnamic acid under superelectrophilic solvation conditions

Article abstract of DOI:10.1016/j.jfluchem.2009.12.006

Friedel-Crafts bimolecular cyclizations of cinnamic acid and cinnamoyl chloride with aromatic compounds in strong and superstrong acids in present of 1 mol% BTISA were investigated. It was demonstrated that catalytic amounts of this new superacid have essential effect on such type of reactions. Its use makes possible the preparation of indanones with quantitative yields.

Full text of DOI:10.1016/j.jfluchem.2009.12.006

Journal of Fluorine Chemistry 131 (2010) 274–277
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Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
BTISA-catalyzed Friedel–Crafts bimolecular cyclization of cinnamic acid under
superelectrophilic solvation conditions
*
Anna G. Posternak, Romute Yu. Garlyauskayte , Lev M. Yagupolskii
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanskaya Str., UA-02094, Kiev, Ukraine
A R T I C L E I N F O
A B S T R A C T
Article history:
Friedel–Crafts bimolecular cyclizations of cinnamic acid and cinnamoyl chloride with aromatic
compounds in strong and superstrong acids in present of 1 mol% BTISA were investigated. It was
demonstrated that catalytic amounts of this new superacid have essential effect on such type of
reactions. Its use makes possible the preparation of indanones with quantitative yields.
ß 2009 Elsevier B.V. All rights reserved.
Received 7 September 2009
Received in revised form 4 December 2009
Accepted 7 December 2009
Available online 16 December 2009
Keywords:
Bis(trifluoromethylsulfonylimino)
trifluoromethansulfonic acid (BTISA)
Superelectrophilic solvation
Indanone
Cinnamic acid cyclization
1. Introduction
Friedel–Crafts bimolecular cyclizations are of our present
interest in view of facts that they are more difficult to effectuate
The use of Brønsted superacids such as TfOH, FSO2OH and their
combinations with superstrong Lewis acids (SbF5, BF3, B(OTf)3)
has received wide propagation for the preparation and study of
many long-lived cationic electrophilic species (carbocations, acyl
and carboxonium cations, onium ions) [1]. It should be stressed
that all conceivable superacids are highly fluorinated compounds
that gives reasons to consider them as an area of fluorine
chemistry. Superelectrophilic solvation, as it was named by Olah
and Klumpp, results in greatly enhanced electrophilic reactivity,
higher reaction rates and allows to put into effect to many unusual
reactions [2].
A radically new superacid—bis(trifluoromethylsulfonylimi-
no)trifluoromethanesulfonic acid (BTISA) was synthesized [3]
under the Yagupolskii principle through the replacement of the
oxygen atoms of TfOH by the 55NSO2CF3 group, and its acid
strength (ÀHo is about 24) was estimated by 29Si NMR
spectroscopy [4]. We recently studied catalysis by the BTISA for
Friedel–Crafts acylation and its advantages over other catalysts
for the electrophilic acylation of aromatic substrates, such as the
selectivity, small amounts (1 mol%) of the acid required, were
demonstrated [5].
and the resulting cyclic aromatic ketones have gained wide-
spread acceptance in the synthesis of pharmaceutical and
natural products [6]. Initially we decided to study the reactivity
of cinnamic acid as model substrate. Previously, this type of
reactions was investigated using aluminium chloride [7],
microwave-assisted/aluminium chloride [8], polyphosphoric
acid [9], H-zeolites [10], and TFA/TFSA systems [11]. As far as
could be determined, good yields of indanone were obtained
under superelectrophilic solvation only requiring great excess of
triflic acid (50–100 equiv.).
The present paper deals with cyclization of cinnamic acid and
cinnamoyl chloride in strong and superstrong acids in the presence
of BTISA.
2. Results and discussion
A relationship between acidity of the system, amounts of the
acid and yields of reaction products (arylation, acylation and
cyclization) was investigated in detail by Klumpp et al. The best
yield of cyclization product (96%) was obtained in the presence of
100 equiv. of TfOH/TFA (45:55) (ÀHo = 11.5) at room temperature
for 12 h [11b].
We studied the reaction of cinnamic acid with benzene in TFA,
H2SO4, and TfOH in the presence of 1 mol% of BTISA (Scheme 1)
under various reaction conditions. The basic data are presented in
Table 1.
* Corresponding author. Tel.: +380 44 559 0349; fax: +380 44 573 2643.
E-mail address: roma@ioch.kiev.ua (R.Yu. Garlyauskayte).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.12.006

A.G. Posternak et al. / Journal of Fluorine Chemistry 131 (2010) 274–277
275
Scheme 1. Cinnamic acid interaction with benzene.
Table 1
Products and yields from the reactions of cinnamic acid with benzene in different acidic systems.
Acid (equiv) + 1% BTISA
Equivalents of benzene
t
(h)
T (8C)
Yield 1aa
Yield 2aa
TFA (100)
TFA (100)
3
2
3
80
15
0
0
0
0
18
H2SO4 (3)
H2SO4 (3)
H2SO4 (6)
H2SO4 (10)
3
3
6
6
12
17
21
21
15
80
80
80
5
76
0
24
39
0
61
100
TfOH (1)
TfOH (1)
TfOH (3)
3
6
3
64
19
42
70
80
15
77
67
0
23
33
100
Without BTISA [11b]
TfOH (3)
11
11
11
12
12
12
25
25
25
47
0
23
TfOH (10)
88 (+9% chalcone)
96
TfOH/TFA 45/55 (100)
0
a
The yields were calculated based on the 1H NMR spectroscopic data.
Scheme 2. Reactions of cinnamic acid with monosubstituted benzenes.
was obtained preferably; (iii) the acylation product was not
observed.
Since 3 equiv. of TfOH with 1 mol% BTISA turned out to be an
optimum acid system, reactions of cinnamic acid with substi-
tuted benzenes have been investigated under these conditions
(Scheme 2). In case of fluoro-, chloro- and bromobenzenes, we
found conditions to obtain the indanones 2(b–d) and 3(b–d) in
quantitative yields (Table 2). The isomers 2(b–d) were formed as
major products and were isolated in pure form. Their
spectroscopic data and melting points agree with literature
It becomes apparent that the addition of just 1 mol% BTISA has a
significant effect on the reaction outcome: (i) 3 equiv. of TfOH are
enough for quantitative yield of indanone 2a; (ii) the reaction takes
place already in H2SO4 (3–6 equiv.), but the arylation product 1a
Table 2
Products and yields of the reactions of cinnamic acid with 3 equiv. of monosubstituted benzenes in TfOH (3 equiv.) in the presence of BTISA (1 mol%).
R
t
(h)
T (8C)
Yield 1a (%)
Yield 2a (%)
Yield 3a (%)
Starting cinnamic acid (%)
F
F
F
19
96
18
16
16
40
35
0
15
14
78
5
4
40
47
0
106
22
Cl
Cl
Cl
15
96
18
15
25
35
29
0
14
53
86
4
18
14
47
0
130
0
Br
16
30
0
82
18
0
a
The yields were calculated based on the 1H NMR spectroscopic data.

276
A.G. Posternak et al. / Journal of Fluorine Chemistry 131 (2010) 274–277
Table 3
Products and yields of the reactions of cinnamic acid with 3 equiv. of chlorobenzenes with BTISA catalysis.
BTISA (equiv.)
t
(h)
T (8C)
Yield 1ca (%)
Yield 2ca (%)
Yield 3ca (%)
Starting cinnamic acid (%)
0.01
0.2
0.2
0.2
3
15
15
18
36
15
2
60
60
70
80
16
70
0
55
60
78
5
0
16
16
16
14
80
0
100
23
18
0
6
6
6
Trace
20
81
0
3
0
a
The yields were calculated based on the 1H NMR spectroscopic data.
Scheme 3. Reaction of cinnamic acid with chlorobenzene under BTISA catalysis.
Scheme 4. Reaction of cinnamoyl chloride with monosubstituted benzenes.
Scheme 5.
data of compounds synthesized by other methods [12]. It has
not been possible to isolate isomers 3(b–d) and to determine
their structures unambiguously. A mixture of more than two
indanone isomers was formed in the reaction of cinnamic acid
with toluene.
In spite of encouraging findings, the study of the reaction with
BTISA alone, without any added TfOH or other acid, was of
fundamental importance. We investigated the reaction of cinnamic
acid with 3 equiv. of chlorobenzene in the presence of different
quantitative of BTISA. As shown in Table 3 1 mol% is not enough to
catalyze any reaction. 20 mol% of BTISA alone is a good catalyst for
the arylation reaction and 3 equiv. are sufficient to conduct the
cyclization under mild conditions in a very short time with
quantitative yield (Scheme 3).
Considering that BTISA is extremely hydroscopic and is used in
very small amounts, it is logical to assume that its reactivity can be
enhanced by using cinnamoyl chloride instead of cinnamic acid
(Scheme 4). Indeed, all reactions take place at room temperature in
shorter reaction time. However, the chalcone is the by-product of
acylation and its yield increased with increasing electron-donor
abilities of the benzenes (Table 4). So, the chalcone is the exclusive
product in case of the cinnamoyl chloride reaction with toluene.
We tested also the reaction with benzotrifluoride, nitrobenzene, 4-
bromofluorobenzene and a mixture of cyclization products was
observed in 1H NMR spectra. We were not able to isolate them
because of side processes like polymerization.
Based on the research performed, it may be proposed that it is
advantageous to synthesize indanones in two steps: the produc-

A.G. Posternak et al. / Journal of Fluorine Chemistry 131 (2010) 274–277
277
Table 4
Products and yields of the reactions of cinnamoyl chloride with 3 equiv. of monosubstituted benzenes in TfOH (3 equiv) and BTISA (1 mol%).
R
t
(h)
T (8C)
Yield 4a (%)
Yield 2a (%)
Yield 3a (%)
H
F
16
16
25
28
26
47
21
33
53
66
55
0
13
13
F
0.5
Cl
Cl
1
26
28
3
60
70
37
20
15
10
CH3
15
26
100
0
a
The yields were calculated based on the 1H NMR spectroscopic data.
tion of 3-phenylcinnamic acid (1a) in sulfuric acid and then its
cyclization in the superacidic system (Scheme 5).
MgSO4 and concentrated on vacuo. The crude product was purified
over silica (hexane:EtOAc, 6:1) and analyzed by NMR.
4.4. Reaction of cinnamoyl chloride with 3 equiv. monosustituted
benzene in TfOH (3 equiv.) and BTISA (1 mol%) acidic systems
3. Conclusions
Based on the research done it may be asserted that BTISA is an
excellent catalyst for use in Friedel–Crafts bimolecular cyclizations
of cinnamic acid or cinnamoyl chloride with aromatic compounds.
The presence of catalytic amount of BTISA under superelectrophilic
solvation conditions has an appreciably influence on the reaction
rate and product yields.
BTISA (4.9 mg, 0.01 mmol) was added to solution of cinnamoyl
chloride (210 mg, 1.3 mmol) in freshly distilled arene (3.7 mmol)
in dry box. Triflic acid (560 mg, 0.33 ml, 3.7 mmol) was slowly
added to the stirred solution at 0 8C. The mixture was heated to
room temperature and allowed to react for a given period of time.
The solution was poured onto ice and extracted with CH2Cl2. The
extract was successively washed with water, NaHCO3 saturated
aquatic solution and a new water, than dried over MgSO4 and
concentrated in vacuo. The crude product was purified over silica
(hexane:EtOAc, 20:1) and analyzed by NMR.
4. Experimental
4.1. General remarks
All reactions were carried out under a dry Ar atmosphere.
Commercially available cinnamic acid was recrystallized from
toluene/hexane (1:1) and dried for 6 h at 25 8C (0.1 mbar).
Cinnamoyl chloride was obtained by reaction of cinnamic acid
with thionyl chloride (5 mole) for 1 h at 80 8C and distilled at 50 8C
(0.1 mbar). Triflic acid was distilled before use at atmospheric
pressure. BTISA was prepared according to a reported procedure
[3] and used as 13% solution in dry CH2Cl2 (P2O5, then CaH2). 1H
and 19F NMR spectra were recorded in CDCl3 on Varian-GeminiVXR
300 (299.9 MHz) and Bruker 200 (188.1 MHz) spectrometers,
respectively.
4.5. Reaction of 3,3-diphenylpropionic acid
Triflic acid (225 mg, 0.13 ml, 1.5 mmol) was added to the stirred
mixture of 3,3-diphenylpropionic acid (113 mg, 0.5 mmol) and
BTISA (2 mg, 0.005 mmol) at room temperature and allowed to
react for 15 h. The solution was poured onto ice and extracted with
CH2Cl2. The extract was successively washed with water, saturated
aquatic NaHCO3 solution and again with water, then dried over
MgSO4 and concentrated in vacuo. The product was distilled. B.p.
110 8C (0.1 mbar).
References
4.2. Reactions of cinnamic acid with benzene in different
acidic systems
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Interscience, New York, 2009.
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therein).
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L.M. Yagupolskii, Org. Biomol. Chem. 3 (2005) 2239–2243 (and references
therein).
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BTISA (11 mg, 0.027 mmol) was added to a mixture of cinnamic
acid (400 mg, 2.7 mmol) and freshly distilled benzene in dry box.
H2SO4 (98%) was added at room temperature. The mixture was
heated to the desired temperature and allowed to react for a given
period of time. The solution was poured onto ice and extracted
with CH2Cl2. The extract was successively washed with water and
brine than dried over MgSO4 and concentrated in vacuo. The crude
product was purified over silica (hexane:EtOAc, 6:1) and analyzed
by NMR.
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BTISA (5.7 mg, 0.01 mmol) was added to mixture of cinnamic
acid (200 mg, 1.3 mmol) and freshly distilled arene (4 mmol) in dry
box. Triflic acid (600 mg, 0.35 ml, 4 mmol) was slowly added at
room temperature. The mixture was heated to the desired
temperature and allowed to react for a given period of time. The
solution was poured onto ice and extracted with CHCl3. The extract
was successively washed with water and brine than dried over
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