Rearrangement of dypnones to 1,3,5-triarylbenzenes

Article abstract of DOI:10.1021/acs.orglett.5b00353

Rearrangement of dypnones to 1,3,5-triarylbenzenes is described. The reaction is proposed to involve an aldol-type self-condensation of dypnones, followed by an intramolecular [2 + 2] cycloaddition and a retro-[2 + 2] cycloaddition. The reaction goes smoothly under obviously milder conditions in comparison to the cyclotrimerization of acetophenones to 1,3,5-triarylbenzenes (10 mol % of TsOH, 80 °C versus 130-148 °C). This unexpected rearrangement would provide new possible considerations in dypnone-involved organic synthesis.

Full text of DOI:10.1021/acs.orglett.5b00353

Letter
pubs.acs.org/OrgLett
Rearrangement of Dypnones to 1,3,5-Triarylbenzenes
Kai Deng,†,§ Qi-Yong Huai,‡,§ Zhi-Lun Shen,† Hui-Jing Li,*,† Chen Liu,† and Yan-Chao Wu*,†
†School of Marine Science and Technology, Harbin Institute of Technology, Weihai 264209, China
‡Marine College, Shandong University, Weihai 264209, China
S
* Supporting Information
ABSTRACT: Rearrangement of dypnones to 1,3,5-triarylbenzenes
is described. The reaction is proposed to involve an aldol-type self-
condensation of dypnones, followed by an intramolecular [2 + 2]
cycloaddition and a retro-[2 + 2] cycloaddition. The reaction goes
smoothly under obviously milder conditions in comparison to
the cyclotrimerization of acetophenones to 1,3,5-triarylbenzenes
(10 mol % of TsOH, 80 °C versus 130−148 °C). This unexpected
rearrangement would provide new possible considerations in
dypnone-involved organic synthesis.
1,3,5-Triarylbenzenes have been a subject of consistent interest
due to their wide range of applications in the fields of special
ligands1 and functional materials including electrode devices,2
resistance materials,3 conducting polymers,4 organic light
emitting diodes,5 etc. Besides, 1,3,5-triarylbenzenes are also
versatile building blocks for the synthesis of polycyclic aromatic
hydrocarbons (PAHs),6 dendrimers,7 and fullerene fragments.8
Accordingly, various synthetic methods have been developed for
the construction of 1,3,5-triarylbenzenes,1−11 which include
substitution of 1,3,5-trihalobenzenes with arylation agents,9 and
cyclotrimerization of acetophenones10/arylethynes.11 Recently,
Jia has developed an elegant cyclotrimerization of acetophenones
to 1,3,5-triarylbenzenes in the presence of p-toluenesulfonic acid
(PTSA, TsOH) at 130−148 °C.10i Here, we would like to report
a new access to 1,3,5-triarylbenzenes via a TsOH-catalyzed
dypnone rearrangement under mild conditions (80 °C).
Scheme 1. Discovery of Dypnone−Triarylbenzene
Rearrangement
The discovery of dypnone-to-triarylbenzene rearrangement
was somewhat serendipitous, which started with our attempts to
synthesize 4H-chromenes from deactivated phenols and
acetophenones. H2SO4-promoted synthesis of 4H-chromenes
from activated phenols and acetophenones at 30−50 °C was
reported.12 Unfortunately, treatment of 4-chlorophenol (1a), a
weak deactivated phenol, with acetophenone (2a) under the
same conditions failed to generate the expected 4H-chromene 3a
(Scheme 1a), in which the annulation of dypnone 4a with phenol
1a did not take place (Scheme 1a−b).12 At higher temperatures
(60−80 °C), 1,3,5-triarylbenzene (5a) instead of 4H-chromene
3a was obtained in 10−15% yields, which was thought to be
formed via the annulation of dypnone 4a with acetophenone 2a
(Scheme 1c).10 To avoid this side reaction, dypnone 4a was
used instead of acetophenone 2a to react with phenol 1a, which
still did not afford 4H-chromene 3a (Scheme 1d). Inspiringly,
dypnone 4a itself was unexpectedly rearranged to 1,3,5-
triarylbenzene 5a at 60−80 °C, even in the absence of phenol
1a (Scheme 1d−e). Considering the potential applications of this
rearrangement in dypnone-involved organic synthesis, we then
turned to optimizing the reaction conditions for the synthesis of
1,3,5-triarylbenzene 5a via the rearrangement of dypnone 4a.
Table 1 lists the representative results. Treatment of 4a in the
presence of concentrated H2SO4 (10 mol %) in toluene (PhMe)
at 80 °C afforded 5a in 63% yield within 12 h (entry 1). Triflu-
oroacetic acid (CF3CO2H), trichloroacetic acid (CCl3CO2H),
acetic acid (CH3CO2H), and formic acid (HCO2H) were not
effective catalysts for this reaction. Treatment of 4a in toluene at
80 °C for 12 h in the presence of these Brønsted acids (10 mol %)
afforded 5a in only 6−13% yields, and most of the starting
material was recovered (entries 2−5). Instead, trifluoromethane-
sulfonic acid (TfOH), benzenesulfonic acid (PhSO3H), 2,4-
dinitrobenzenesulfonic acid (DNBSA), and TsOH displayed
good efficiency for this reaction, which afforded 5a in 71−88%
yields under otherwise the same conditions (entries 6−9).
Unsurprisingly, the reaction did not work in the absence of a
Received: February 3, 2015
Published: March 5, 2015
© 2015 American Chemical Society
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DOI: 10.1021/acs.orglett.5b00353
Org. Lett. 2015, 17, 1473−1476

Organic Letters
Letter
dypnones bearing hydrogen atoms (entry 1), electron-with-
drawing groups (entries 2−5), and electron-donating groups
(entries 6−9), rearrangement of dypnones 4a−i went smoothly
in the presence of TsOH (10 mol %) at 80 °C to afford 1,3,5-
triarylbenzenes 5a−i in excellent yields within 12 h. Rearrange-
ment of dypnone 4j went uneventfully to afford 1,3,5-
triarylbenzenes 5j in 62% yield under the standard conditions,
albeit at 60 °C within 24 h (entry 10). No reaction took place
when 4′-benzyloxyacetophenone was used instead of dypnone 4j
under otherwise the same conditions, and debenzylation was
observed when the temperature exceeded 80 °C. The result
indicated that, in contrast to the cyclotrimerization of aceto-
phenones, the present protocol is milder and thus could tolerate
more functional and protecting groups. 3,3′-Dichlorodypnone
(4k) and 3,3′-dimethyldypnone (4l) underwent rearrangement
under the standard conditions to afford 1,3,5-triarylbenzenes
5k and 5l in 68% and 81% yields, respectively (entries 11−12).
2,2′-Dimethyldypnone (4m), a relatively sterically hindered
dypnone, underwent rearrangement uneventfully under the
standard conditions to generate 1,3,5-triarylbenzene 5m in a
moderate yield (entry 13). 3,3′,4,4′-Tetramethyldypnone (4n)
has also been investigated, which underwent rearrangement
under the standard conditions to afford 1,3,5-triarylbenzene
5n in 61% yield (entry 14). These reactions are very easy to
perform without the need to use anhydrous solvent and an inert
atmosphere.
Table 1. Survey of Conditions for the Rearrangement of
Dypnone (4a) to 1,3,5-Triarylbenzene (5a)
a
entry
catalyst
H2SO4
solvent
PhMe
temp
yield
1
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
130 °C
60 °C
70 °C
90 °C
80 °C
80 °C
63%
13%
12%
6%
2
CF3CO2H
CCl3CO2H
CH3CO2H
HCO2H
TfOH
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
DMF
H2O
EtOH
CH3NO2
n-hexane
1,4-dioxane
DCE
−
3
4
5
11%
71%
81%
83%
88%
0
6
7
PhSO3H
DNBSA
TsOH
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
−
Fe(OTf)3
73%
5%
FeCl3
Fe2(SO4)3
Bi(OTf)3
TsOH
3%
76%
trace
trace
53%
73%
83%
85%
90%
93%
18%
91%
67%
88%
91%
82%
92%
TsOH
TsOH
TsOH
TsOH
Acetophenone 2a could be detected in the TsOH-catalyzed
rearrangement of dypnone 4a to 1,3,5-triarylbenzene 5a.
Treatment of acetophenone 2a with an equal equivalent of
dypnone 4a in the presence of TsOH at 80 °C afforded 1,3,5-
triarylbenzene 5a in 85% yield within 12 h (Scheme 2), in which
TsOH
TsOH
TsOH
b
23
TsOH
−
−
−
−
−
−
−
b
24
TsOH
25
26
27
TsOH
TsOH
Scheme 2. Reaction of Acetophenone 2a with Dypnone 4a
TsOH
c
28
TsOH
d
29
TsOH
a
General conditions: 4a (1.0 mmol) and catalyst (0.1 mmol) in
solvent (0.2 mL) for 12 h. DNBSA: 2,4-dinitrobenzenesulfonic
b
acid. Acetophenone (2a, 2.0 mmol) was used instead of dypnone
c
d
(4a). 5 mol % of TsOH was used. Reaction was carried out at 2.22 g
dypnone 4a was completely converted to 1,3,5-triarylbenzene 5a
whereas nearly 20% of acetophenone 2a remained. As mentioned
in Table 1 (entry 23), the cyclotrimerization of acetophenone 2a
went slowly at 80 °C. Therefore, the reaction of acetophenone 2a
with dypnone 4a in the presence of TsOH at 80 °C should
include processes of dypnone rearrangement and acetophe-
none−dypnone annulation.
Based on the above results, a possible reaction mechanism for
the rearrangement of dypnones 4 to 1,3,5-triarylbenzenes 5 is
illustrated (Scheme 3). Dypnones 4 undergo an enolization
followed by an aldol-type addition with dypnones 4 and a
subsequent dehydration to form the intermediates 8, which are
converted to 1,3,5-triarylbenzenes 5 and acetophenones 2 via an
intramolecular [2 + 2] cycloaddition and a subsequent retro-[2 +
2] cycloaddition. On the other hand, an aldol-type condensation
of acetophenones 2 with compounds 6 followed by subsequent
dehydration and an enolization generates the intermediates 11,
which undergo a 6π-electrocyclization and a dehydration to
afford 1,3,5-triarylbenzenes 5.10
scale of 4a (10.0 mmol) under an air atmosphere.
catalyst (entry 10). TsOH is the most efficient catalyst for this
reaction in all screened Brønsted acids and Lewis acids (entries
1−9, 11−14). With the use of N,N-dimethylformamide (DMF),
water (H2O), ethanol (EtOH), nitromethane (CH3NO2),
n-hexane, and 1,4-dioxane in comparison to toluene, relatively
lower yields were observed (entries 9 and 15−20). Fortuitously,
5a was obtained in excellent yields when the reaction was
performed in 1,2-dichloroethane (DCE) or under solvent-free
conditions (entries 21−22). When acetophenone (2a, 2.0 mmol)
was used instead of dypnone (4a, 1.0 mmol), an obviously higher
reaction temperature was required (entries 22−24).10i Further
parameter optimization identified 80 °C as the most effective
reaction temperature (entries 22, 25−27). The reaction went
well when the loading of TsOH was not less than 10 mol %
(entries 22, 28). Furthermore, by scaling up 4a to 2.22 g the
reaction provided the yield at an excellent level, which was easy to
perform under an air atmosphere (entry 29).
In summary, we have developed an unprecedented dypnone-
to-triarylbenzene rearrangement under metal- and solvent-free
conditions, which provided a mild, facile, and environmentally
benign approach for the synthesis of 1,3,5-triarylbenzenes, a
With the optimized reaction conditions in hand, the scope of
the reaction was subsequently investigated, and the representa-
tive results are summarized in Table 2. With the aromatic rings of
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DOI: 10.1021/acs.orglett.5b00353
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Organic Letters
Letter
a
Table 2. Rearrangement of Dypnones 4 to 1,3,5-Triarylbenzenes 5
a
b
General conditions: 4 (1.0 mmol) and TsOH (0.1 mmol) at 80 °C for 12 h. The reaction was performed at 60 °C for 24 h.
Scheme 3. Proposed Mechanism
ASSOCIATED CONTENT
* Supporting Information
■
S
General experimental procedure and characterization data of the
products. This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: lihuijing@iccas.ac.cn.
*E-mail: ycwu@iccas.ac.cn.
Author Contributions
§K.D. and Q.-Y.H. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Science and Technology
Development Project of Weihai (2011DXGJ13, 2012DXGJ02),
the Natural Science Foundation of Shandong (ZR2012BM002),
and the National Natural Science Foundation of China
(21272046).
privileged motif found in a large number of special ligands and
functional materials. Synthetic applications of this reaction are
under investigation.
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DOI: 10.1021/acs.orglett.5b00353
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Organic Letters
Letter
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