Bromination of hydrocarbons with CBr4, initiated by light-emitting diode irradiation

Article abstract of DOI:10.3762/bjoc.9.190

The bromination of hydrocarbons with CBr₄ as a bromine source, induced by light-emitting diode (LED) irradiation, has been developed. Monobromides were synthesized with high efficiency without the need for any additives, catalysts, heating, or inert conditions. Action and absorption spectra suggest that CBr₄ absorbs light to give active species for the bromination. The generation of CHBr₃ was confirmed by NMR spectroscopy and GC-MS spectrometry analysis, indicating that the present bromination involves the homolytic cleavage of a C-Br bond in CBr₄ followed by radical abstraction of a hydrogen atom from a hydrocarbon.

Full text of DOI:10.3762/bjoc.9.190

Bromination of hydrocarbons with CBr4,
initiated by light-emitting diode irradiation
Yuta Nishina*1, Bunsho Ohtani2 and Kotaro Kikushima1
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2013, 9, 1663–1667.
1Research Core for Interdisciplinary Science, Okayama University,
Tsushimanaka, Kita-ku, Okayama 700-8530, Japan and 2Catalysis
Research Center, Hokkaido University, Sapporo 001-0021, Japan
doi:10.3762/bjoc.9.190
Received: 26 April 2013
Accepted: 25 July 2013
Published: 14 August 2013
Email:
Yuta Nishina* - nisina-y@cc.okayama-u.ac.jp
This article is part of the Thematic Series "Organic free radical chemistry".
Guest Editor: C. Stephenson
* Corresponding author
Keywords:
bromination; free radical; hydrocarbon; light-emitting diode; photo
irradiation
© 2013 Nishina et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
The bromination of hydrocarbons with CBr4 as a bromine source, induced by light-emitting diode (LED) irradiation, has been
developed. Monobromides were synthesized with high efficiency without the need for any additives, catalysts, heating, or inert
conditions. Action and absorption spectra suggest that CBr4 absorbs light to give active species for the bromination. The generation
of CHBr3 was confirmed by NMR spectroscopy and GC–MS spectrometry analysis, indicating that the present bromination
involves the homolytic cleavage of a C–Br bond in CBr4 followed by radical abstraction of a hydrogen atom from a hydrocarbon.
Introduction
Bromination reactions of organic compounds are fundamental efforts have been focused on benzylic bromination using Br2 or
reactions for providing a wide variety of organic precursors for bromide salts as highly efficient bromine sources [13-17].
industrial materials [1-8]. Generally, the bromination of satu- However, the direct bromination of non-activated C–H bonds is
rated hydrocarbons proceeds through radical abstraction of still a challenging task. Although Br2 [13], CBr4 [18-20],
hydrogen atoms and trapping with bromide, whereas the bro- R4NBr [21,22] and LiBr [23] have been reported to serve as
mination reactions of aromatic and unsaturated hydrocarbons bromine sources for the bromination of saturated hydrocarbons,
are induced by electrophilic addition of bromine and/or a these reactions exhibit low selectivity or reactivity. Efficient
cationic bromide. Combinations of N-bromosuccinimide (NBS) bromination using Br2 as a bromine source combined with a
with azobisisobutyronitrile or benzoyl peroxide as radical initia- stoichiometric base [24], an excess of MnO2 [25], or a catalytic
tors are typical conditions for Wohl–Ziegler bromination [9-12] amount of Li2MnO3 [26] has been reported to give high reactiv-
and are widely used for the bromination of benzylic and allylic ity and selectivity. The combination of CBr4 with a copper cata-
positions, despite the need for heating and the generation of lyst at high temperature also achieves effective bromination of
equimolar amounts of waste. To avoid these drawbacks, several hydrocarbons [27].
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Beilstein J. Org. Chem. 2013, 9, 1663–1667.
We have focused on CBr4, which is solid and easy to handle, as yield reached 148% and had almost peaked (Table 1, entry 3).
a bromine source. CBr4 has been used in organic synthesis to Further improvements were not observed, even after 24 h
give useful bromide-containing precursors. For instance, alkyl (Table 1, entry 5). These results indicate that during the reac-
alcohols can be converted to alkyl bromides in the presence of tion one or more bromine atoms originated from one CBr4. It is
CBr4 and triphenylphosphine; this is known as the Appel reac- considered that CHBr3 generated through radical abstraction of
tion [28]. This combination can also be used to transform alde- a hydrogen atom by a tribromomethyl radical served as a
hydes into dibromoalkenes, which are useful precursors for the bromine source. To test this hypothesis the reaction was
Corey–Fuchs reaction [29], to obtain terminal alkynes. repeated with CHBr3 instead of CBr4 and the product was
Although CBr4 has been used for various bromination reactions obtained in a low yield (Table 1, entry 6), whereas the reaction
including radical brominations, these reactions need further with CH2Br2 produced no bromination product at all under
additives to proceed. Here, we disclose the efficient bro- these conditions (Table 1, entry 7). Other bromination reagents
mination of saturated hydrocarbons, using CBr4 as a bromine such as NBS also gave the desired product in moderate yield
source without any additives, through radical reactions induced (Table 1, entry 8). In the case of tetrabutylammonium bromide,
by irradiation with light from commonly used light-emitting no brominated product was obtained (Table 1, entry 9), showing
diodes (LEDs) [30]. In this reaction, additives, catalysts, that the present reaction was a radical reaction. Based on the
heating, and inert reaction conditions are all unnecessary. assumption that the initial formation of bromine radicals would
be important, addition of catalytic amounts of CBr4 along with
Results and Discussion
various bromination sources was examined (Table 1, entries
First, the bromination of cyclohexane under LED irradiation 10–12). The combination of catalytic CBr4 with CHBr3 or
was investigated using 1.0 mL of cyclohexane with 0.20 mmol CH2Br2 resulted in slight improvements in the yields (Table 1,
CBr4 (Table 1). The desired monobrominated product was entries 10 and 11), showing these bromides also could serve as
obtained in 77% yield, based on CBr4, after 2 h, and no dibro- bromination sources in the presence of the radical species. The
mide was observed (Table 1, entry 1). It was found that the combination of CBr4 with NBS gave the desired product in a
yield of cyclohexyl bromide exceeded 100% after 3 h (Table 1, moderate yield (Table 1, entry 12). On the other hand, the reac-
entry 2). When the mixture was irradiated for 4 h, the product tion was inhibited by the addition of water (Table 1, entry 13)
and performing the reaction under inert argon atmosphere led to
a decreased yield of 87% (Table 1, entry 14).
Table 1: Bromination of cyclohexane using CBr4 under LED irradi-
ation.a
Based on the above experiments, the bromination of other
substrates was examined with CBr4 under LED irradiation.
Cyclooctane underwent bromination under the optimized condi-
tions to furnish the monobromide in 178% yield, based on
CBr4, without contamination by dibromide (Table 2, entry 1).
entry
bromination source (mmol)
time (h) yield (%)b
The bromination of n-hexane produced three bromides:
1-bromohexane (14%), 2-bromohexane (84%), and 3-bromo-
hexane (41%) (Table 2, entry 2). On the other hand, no bro-
mination of toluene occurred under LED irradiation. In this
case, light would be absorbed by the aromatic ring of toluene,
suppressing the activation of CBr4. Using sunlight in place of
LED light, however, resulted in the bromination of the benzylic
position to give benzyl bromide in 140% yield (Table 2,
entry 3).
1
CBr4 (0.20)
2
77
108
148
148
150
27
0
2
CBr4 (0.20)
3
3
CBr4 (0.20)
4
4
CBr4 (0.20)
5
5
CBr4 (0.20)
24
24
24
24
24
24
24
24
24
24
6
CHBr3 (0.20)
7
CH2Br2 (0.20)
NBS (0.20)
8
31
0
9
Bu4NBr (0.20)
CBr4 (0.02)/CHBr3 (0.20)
CBr4 (0.02)/CH2Br2 (0.20)
CBr4 (0.02)/NBS (0.20)
CBr4 (0.20)
10
11
12
13c
14d
39
16
79
0
To investigate the wavelength dependency of the present reac-
tion, the action spectrum of the bromination of cyclohexane in
the presence of CBr4 was obtained by plotting the apparent
quantum efficiency against wavelength (Figure 1, red line) [31].
It was found that the present reaction was promoted by irradi-
ation with ultraviolet (UV) light and deactivated under visible-
light (>475 nm) irradiation. CBr4 shows strong absorption in
the UV region (Figure 1, blue line), and this overlaps with the
CBr4 (0.20)
87
aConditions: 1.0 mL of cyclohexane, bromination sources, under LED
irradiation, rt. bYields were determined by GC analysis based on the
mole of CBr4. cIn the presence of 0.10 mL water. dUnder Ar.
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Beilstein J. Org. Chem. 2013, 9, 1663–1667.
A plausible mechanism for the present bromination is illus-
trated in Scheme 1. First, photo-irradiation generates a bromine
radical and a CBr3 radical (Scheme 1, reaction 1), which
abstracts a hydrogen atom from the substrate to form CHBr3
(Scheme 1, reaction 2). Finally, the radical species derived from
the substrate reacts with the bromine radical or CBr4 to afford
the brominated product (Scheme 1, reactions 3 and 4). Addi-
tionally, the in situ generated CHBr3 releases a bromine radical
upon LED irradiation, thus serving as a bromine source
(Scheme 1, reaction 5). Alternatively the radical species derived
from the substrate abstracts a bromine atom from CHBr3
(Scheme 1, reaction 6).
Table 2: Bromination of other substrates using CBr4 under LED irradi-
ation.a
entry
1
substrate
product
yield (%)
178
2
14
84
41
3
140b
aConditions: 1.0 mL of substrate, 0.20 mmol of CBr4, under LED irradi-
ation. Yields were determined by GC using dodecane as an internal
standard. bUnder sunlight irradiation.
above-mentioned action spectrum. The activation of CBr4 is
therefore considered to be induced by photo-irradiation, initi-
ating the reaction. Although other light sources could also acti-
vate CBr4, we adopted LED light due to safety, mildness, and
availability. We have confirmed that fluorescent room light
could also promote the reaction.
Scheme 1: Plausible mechanism for bromination of cyclohexane with
CBr4 induced by LED irradiation.
Figure 1: Action spectrum of bromination with CBr4, induced by LED irradiation (red line), and absorption spectrum of CBr4 (blue line).
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Beilstein J. Org. Chem. 2013, 9, 1663–1667.
Figure 2: 13C NMR monitoring of reaction mixtures: (a) 0.50 mmol of CBr4, 0.10 mL of cyclohexane, and 0.40 mL of CDCl3, (b) 0.5 mmol of CHBr3,
0.10 mL of cyclohexane, and 0.40 mL of CDCl3, (c) 0.50 mmol of CBr4 and 0.10 mL of cyclohexane, LED irradiation for 24 h, and then addition of
0.40 mL of CDCl3.
To examine the above hypothesis, the bromination of cyclo- CBr4 to generate bromine radicals, which initiate the bro-
hexane was monitored using 13C NMR spectroscopy (Figure 2). mination reaction. Further elucidation of the detailed mecha-
CBr4 (0.50 mmol) dissolved in cyclohexane (0.10 mL) and nism and the use of LED irradiation in other reaction systems
CDCl3 (0.40 mL) was observed at −29.7 ppm (Figure 2a). After are under investigation in our laboratory.
stirring a reaction mixture of CBr4 (0.50 mmol) and cyclo-
Experimental
hexane (0.10 mL) under LED irradiation for 24 h, peaks
assigned to bromocyclohexane (53.4, 37.6, 25.9, and 25.1 ppm) General information
and another strong peak at 9.6 ppm appeared (Figure 2c). The All commercially available compounds were purchased and
latter peak was found to be consistent with the peak of CHBr3 used as received. Cyclohexane, cyclooctane, n-hexane, and
(0.50 mmol) dissolved in cyclohexane (0.10 mL) and CDCl3 toluene were purchased from Wako Pure Chemical Industries
(0.40 mL) (Figure 2b). Additionally, the generation of CHBr3 in and used as received. 1H (400 MHz) and 13C (100 MHz) NMR
the present bromination was confirmed by 1H NMR spec- spectra were recorded using a JEOL JNM-LA400 spectrometer.
troscopy and GC–MS spectrometry. These results support the Proton chemical shifts are reported relative to residual solvent
reaction pathway described above, although the chemical peak of CDCl3 at δ 7.26 ppm. Carbon chemical shifts are
species after the second bromination was not assigned at this reported relative to CDCl3 at δ 77.00 ppm. Gas chromato-
point.
graphic analysis was conducted with Shimadzu GC-2014
equipped with FID detector. The chemical yields were deter-
mined using dodecane as an internal standard. The NMR data of
Conclusion
In conclusion, we have developed a method for the hydro- all brominated products match those reported.
carbon bromination induced by LED irradiation using CBr4 as a
General procedure for the bromination
bromine source. The present reaction system did not require any
additives, catalysts, heating, or inert conditions, and is there- induced by LED irradiation
fore an extremely simple procedure. An action spectrum and A reaction tube was charged with CBr4 (66.33 mg, 0.20 mmol)
NMR measurements showed that the LED irradiation activates and a hydrocarbon (1.0 mL). The reaction mixture was stirred
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Beilstein J. Org. Chem. 2013, 9, 1663–1667.
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Acknowledgements
Financial support for this study was provided by the Develop-
ment of Human Resources in Science and Technology, The
Circle for the Promotion of Science and Engineering, and the
Cooperative Research Program of Catalysis Research Center,
Hokkaido University (Grant #11B2001). We also received
generous support from Mr. Junya Miyata, Mr. Ryota Watanabe,
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