Microwave-Assisted Dibromoolefination of Aromatic and Heteroaromatic Aldehydes and Ketones

Article abstract of DOI:10.1002/jhet.2332

Microwave (MW) irradiation was successfully employed to convert aromatic and heteroaromatic aldehydes and ketones efficiently to the corresponding dibromoolefins. Exemplified by the successful dibromoolefination of traditionally inert pyridyl-flanked carbonyls, MW activation significantly broadens the scope of this valuable transformation, although some limitations especially with electron-rich aromatic ketone derivatives remain.

Full text of DOI:10.1002/jhet.2332

Month 2015 Microwave-Assisted Dibromoolefination of Aromatic and Heteroaromatic
Aldehydes and Ketones
Djawed Nauroozi, Clemens Bruhn, Sven Fürmeier, Jörn-Uwe Holzhauer, and Rüdiger Faust
†
*
Institute for Chemistry and CINSaT—Center for Interdisciplinary Nanostructure Science and Technology,
University of Kassel, Heinrich-Plett-Str. 40, 34132 Kassel, Germany
†Current address: Institut für Organische Chemie II und Neue Materialien, Albert-Einstein-Allee 11, 89081 Ulm, Germany
*
E-mail: r.faust@uni-kassel.de
Additional Supporting Information may be found in the online version of this article.
Received May 5, 2014
DOI 10.1002/jhet.2332
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
Microwave (MW) irradiation was successfully employed to convert aromatic and heteroaromatic
aldehydes and ketones efficiently to the corresponding dibromoolefins. Exemplified by the successful
dibromoolefination of traditionally inert pyridyl-flanked carbonyls, MW activation significantly broadens
the scope of this valuable transformation, although some limitations especially with electron-rich aromatic
ketone derivatives remain.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
dibromoolefination of pyridyl-based ketones. Conspicu-
ously, dibromoolefins from pyridyl-flanked carbonyl
derivatives have not been reported before. Indeed, attempts
to convert diazafluoren-9-one 1 [21] to the corresponding
dibromoolefin under standard Corey–Fuchs conditions
even at elevated temperatures for extended periods of time
(reflux in xylenes for 5 h) failed. Inspired by many reports
on successful thermal activation of organic transformations
by microwave irradiation [22], we submitted ketone 1
together with CBr4 and PPh3 in CH2Cl2 for 20min at 80°C
in a sealed reaction vessel to microwave irradiation of
100 W. Much to our satisfaction, the desired dibromoolefin
3 was obtained in 55% yield (Scheme 1). Remarkably, the
product was purified by a simple flash filtration of the
reaction mixture through a plug of silica followed by
recrystallization of the crude product from acetone. Under
identical conditions, the less rigid di-2-pyridylketone 2 was
transformed to the corresponding dibromoolefin 4 in even
higher yields (65%).
The conversion of aldehydes and ketones into the
corresponding gem-dihaloolefins is a valuable functional
group transformation [1] that delivers versatile intermediates
for the synthesis of, inter alia, amides [2], ynamides [3],
ketene N,N-acetals [4], 2-bromo-indoles [5], alkynyl
methylidenes [6], 1-alkenyl-phosphonates [7] or allylsilanes
[8]. gem-Dihaloolefins can also be used as starting materials
in transition-metal-mediated CC cross-coupling reactions
[9–11]. Perhaps the currently most prominent application
lies in their suitability as a source for oligoalkynes by way
of the Fritsch–Buttenberg–Wiechell rearrangement [12].
Dibromoolefins are routinely prepared from carbonyl
compounds using CBr4 and PPh3 in a Wittig-type reaction
first reported by Ramirez et al. [13,14] and subsequently
with some variation by Corey and Fuchs [15]. More
recently, a metal-induced modification with CHBr3/TiCl4/
Mg was used for such a transformation [16]. It was also
shown that a perchlorate phosphine salt [17] as well as
triisopropyl phosphite can replace PPh3 in generating
gem-dihaloolefins [18]. These reactions, in general, run
smoothly and in good yields with most aldehydes. However,
the yields with less reactive ketones varies, and often, as in
the case of benzophenone, no conversion is observed [19].
The identity of the new dibromoolefins was confirmed
by spectroscopic techniques and mass spectrometry (for
details, refer to the Supporting Information). Unambiguous
proof for the constitutions of both 3 and 4 was established
by investigating their crystal structures under X-ray
diffraction conditions [23].
As can be seen in Figure 1, the rigidity of 3 imposes an
almost ideal planar conformation and gives rise to a
herringbone arrangement of molecules of 3 in the solid
state. That pattern is formed by a crystallographic gliding
RESULTS AND DISCUSSION
Our ongoing research on molecular wires with appending
metal fragments [20] prompted us to explore the
© 2015 HeteroCorporation

D. Nauroozi, C. Bruhn, S. Fürmeier, J.-U. Holzhauer, and R. Faust
Vol 000
Scheme 1. MW-assisted dibromoolefination of ketones 1 and 2.
Figure 1. Crystal structure of 3 and its herringbone arrangement in the unit cell. [Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
plane along c that can be seen in a view of the unit cell along
the b-axis. The packing reveals π-stacking interactions
within the layers with a minimum distance of 3.222(7) Å
between them. The structure of 4 in the solid state reveals sim-
ilar features and is discussed in the Supporting Information.
Encouraged by this success, we explored the scope
of the microwave-assisted dibromoolefination with
aromatic and heteroaromatic aldehydes and ketones
(Table 1). In general, the results suggest that the conver-
sion of carbonyl compounds flanked by relatively
electron-poor aromatic substituents benefits from
microwave irradiation. Electron-rich substituents seem to
decrease the yields of the corresponding dibromoolefins.
In the aldehyde series (entries 1–5 in Table 1), yields
under microwave activation are either comparable or
better than the conventional Corey–Fuchs conditions.
While the yields are satisfactory with benzaldehyde,
p-nitrobenzaldehyde, and 2-pyridylcarbaldehyde, the
aldehydes flanked by the electron-rich substituents
4-dimethylaminophenyl, 2-thienyl, and 2-pyrryl give
moderate yields or, in the latter case, no conversion. A
similar trend was observed in the ketone series (entries 6–12,
Table 1) as it can be seen in the poor to moderate conversion
yields of 2-benzoylpyridine and the bis(2-thienylethynyl)
ketone, respectively. However, the microwave-assisted
dibromoolefination shows its superiority in the successful
conversion of diazafluoren-9-one and di-2-pyridylketone
as well as 2-benzoylpyridine, which could not be obtained
otherwise. There are reports in the literature [24] about a
high yielding dibromoolefination of thioxanthene-9-one in
refluxing benzene at 150°C for 44 h. In our hands, the
transformation was only successful under microwave
assistance. Furthermore, compounds with two carbonyl
centers (anthraquinone and 2,5-diacetylpyridine) could
easily be transformed into the corresponding dibromo-
olefins with simply doubling the amount of the reagents.
The cleanliness of the conversion and the less harmful
solvent CH2Cl2 used under the given conditions render this
procedure a valuable alternative. In line with our observed
trend, attempts to convert benzophenone or fluorenone
failed under conventional conditions as well as under
microwave irradiation.
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Microwave-Assisted Dibromoolefination of Aromatic
and Heteroaromatic Aldehydes and Ketones
Table 1
Conversion of aldehydes and ketones into dibromoolefins using microwave irradiation.a
Entry
1
Aldehyde or ketone
Dibromoolefin
Yield (%)
75
2
3
95
20
4
5
73
75
6
7
91
80
8
9
65
55
10
11
23
41
12
85
aMicrowave conditions are CBr4, PPh3, CH2Cl2, 80°C, 3.5 bar, 100 W, and 20 min.
Journal of Heterocyclic Chemistry
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D. Nauroozi, C. Bruhn, S. Fürmeier, J.-U. Holzhauer, and R. Faust
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1,1-Dibromo-2,2-di(2-pyridyl)ethene (4).
Yield 360 mg (65%), colorless needles.
mp 120°C (recrystallization from acetone).
In conclusion, we could show that the microwave-assisted
dibromoolefination is a convenient method for the
conversion of aromatic and heteroaromatic aldehydes and
ketones into the corresponding dibromoolefins. As typically
observed in microwave reactions, the method is character-
ized by short reaction times and clean transformations with
a facile purification of products. Particularly noteworthy is
the successful conversion of pyridyl-substituted aldehydes
and ketones into their corresponding dibromoolefins, which
will prove helpful in the design of new cross-conjugated
ligand systems to transition metal fragments.
1H-NMR δ = 8.60 (ddd, J = 4.2, 2.7, and 0.7 Hz, 2 H), 7.75
(dd, J = 6.1 and 1.4 Hz, 2 H), 7.65 (dd, J = 7.8 and 1.7 Hz, 2H),
7.24 (ddd, J = 5.1, 4.2, and 1.5 Hz, 2H).
13C-NMR δ = 157.85, 149.54, 146.18, 136.93, 125.06, 123.11,
96.08.
HRMS/ESI (+) m/z= 338.9125, calculated (C12H9Br2N2) = 338.9127.
1,1-Dibromo-2-(2-pyridyl)-2-phenylethene (Table 1, entry 10).
Yield 128 mg (23%), yellow oil.
1H-NMR δ = 8.64 [s (br), 1H], 7.71 (dd, J= 1.46 and 7.76 Hz, 1H),
7.41–7.30 (m, 7H).
13C-NMR δ = 158.65, 149.23, 146.53, 139.84, 137.26, 131.12, 129.05,
127.32, 124.43, 122.97, 93.78.
EXPERIMENTAL
MS/ESI (+)m/z= 340.
All chemicals were purchased from commercial suppliers and
2,6-Bis(1,1-dibromoprop-1-en-2-yl)pyridine (Table 1, entry 12).
Yield 740 mg (85%), yellow oil.
used without further purification. CH2Cl2 for synthesis was dried
1
over CaH2. H-NMR and 13C-NMR spectra were recorded on a
1H-NMR δ =7.71 (t, J= 7.74 Hz, 1H), 7.27 (d, J= 7.79 Hz, 2H), 2.26
(s, 6H).
500 or 400-MHz Varian spectrometer (1H 500/400 MHz, 13C
125/100 MHz) using CDCl3 or tetrahydrofuran (THF)-d8 as the
solvent with tetramethylsilane (TMS) as the internal standard at
room temperature. Chemical shifts are given relative to TMS;
the coupling constants J are given in Hz. Mass spectra were
recorded on a Finnigan LCQ DECA (ThermoQuest) using
an atmospheric pressure chemical ionization technique. The
high-resolution mass spectrometry (HRMS) was recorded on a
time of light spectrometer (micrOTOF—Bruker Daltonics) using
an Apollo “Ion Funnel” electrospray ionization (ESI) as the ion
source. Melting points were determined with a Büchi M-565
apparatus and are uncorrected. Microwave reactions were run
on a CEM Discover SP or Biotage Initiator Classic, each
monomode apparatus. All known compounds (Table 1, entries
1 [25], 2 [26], 3 [27], 5 [28], 6 [29], 7 [24], and 11 [30]) afforded
analytical data identical to those reported in literature (refer to
Supporting Information for further details).
13C-NMR δ = 159.02, 142.29, 137.00, 122.43, 90.54, 29.78.
MS/ESI (+) m/z= 475.
Acknowledgments. We thank M. Wrazidlo for assistance in some
of the experiments as well as Sascha Ott and Anna Arkhypchuk for
providing some chemicals.
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Typical procedure.
Diazafluoren-9-one 1 [21] (300 mg,
1.65 mmol), CBr4 (2 equiv, 1.09 g, 3.29 mmol), and PPh3 (4 equiv,
1.73 g, 6.59 mmol) were placed into a microwave vial, which was
purged with argon (in case of bis-dibromoolefination, twice the
amount of the reagents was used). Dry CH2Cl2 was added to the
mixture, and the vial was capped tightly and put into the microwave
reactor (CEM Discover SP or Biotage Initiator Classic). After 20-
min irradiation (80°C, 3.5-bar internal pressure, 100 W), the reaction
mixture was cooled and poured onto a plug of silica gel. The silica
gel was washed with an additional amount of CH2Cl2 (100 mL)
before the eluate was evaporated on the rotary evaporator to dryness.
The pure product was obtained by recrystallization from acetone to
furnish 3 (310 mg, 55%) as colorless needles.
9H-Dibromomethylene-4,5-diazafluorene (3).
Yield 310 mg (55%), colorless needles.
mp 164°C (recrystallization from acetone).
1H-NMR (CDCl3) δ = 8.79 (dd, J = 5.0 and 1.5 Hz, 2 H), 7.99
(dd, J = 7.5 and 1.5 Hz, 2 H), 7.35 (dd, J = 7.1 and 4.8 Hz, 2H).
1H-NMR (THF-d8) δ = 8.96 (dd, J = 8.2 and 1.0 Hz, 2 H), 8.69
(dd, J = 4.7 and 1.3 Hz, 2H), 7.37 (dd, J = 8.2 and 4.7 Hz, 2H).
13C-NMR (CDCl3) δ = 157.15, 155.14, 150.76, 132.56, 131.41,
123.00, 95.14.
13C-NMR (THF-d8) δ = 158.77, 151.81, 135.67, 134.02, 133.17,
123.74, 95.74.
HRMS/ESI (+) m/z= 336.8977, calculated (C12H7Br2N2) = 336.8971.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Microwave-Assisted Dibromoolefination of Aromatic
and Heteroaromatic Aldehydes and Ketones
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