Oxidative bromination reactions in aqueous media by using Bu4NBr/TFA/H2O2 system

Article abstract of DOI:10.1246/cl.170734

Metal-free oxidative bromination reactions in aqueous media were performed using tetrabutylammonium bromide, trifluoroacetic acid, and hydrogen peroxide under mild conditions. Oxidative bromination reaction of alkenes was found to afford the corresponding vic-bromides. Furthermore, this oxidative bromination system is applicable to the oxidative bromination of alkynes, arenes, and 3,4-dihydronaphthalen-1(2H)-one. A gram-scale bromination reaction was also performed successfully.

Full text of DOI:10.1246/cl.170734

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Oxidative Bromination Reactions in Aqueous Media by Using Bu NBr/TFA/H O System
Toshiyuki Moriuchi,* Yasuhiro Fukui, Takashi Sakuramoto, and Toshikazu Hirao*
Advance Publication on the web August 31, 2017
doi:10.1246/cl.170734
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2017 The Chemical Society of Japan
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1
Oxidative Bromination Reactions in Aqueous Media by Using Bu
4
NBr/TFA/H
2
O System
2
Toshiyuki Moriuchi,* Yasuhiro Fukui, Takashi Sakuramoto, and Toshikazu Hirao*
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Yamada-oka, Suita, Osaka 565-0871
(
moriuchi@chem.eng.osaka-u.ac.jp and hirao@chem.eng.osaka-u.ac.jp)
Dedicated to the late Professor Yoshihiko Ito on the occasion of the 10th anniversary of his sudden death.
Metal-free oxidative bromination reactions in aqueous
The oxidative bromination reaction of 1-decene with 200
mol% Bu NBr, 300 mol% TFA, and 300 mol% H in an
ultrapure water was investigated (Table 1). The bromination
reaction proceeded at 25 °C to afford the corresponding vic-
dibromide 1 in 78% yield (Entry 1). A decrease in the amount
of TFA resulted in a gradual decrease of the yields (Entries 2-
media were performed by using tetrabutylammonium bromide,
trifluoroacetic acid, and hydrogen peroxide under mild
conditions. Oxidative bromination reaction of alkenes was
found to afford the corresponding vic-bromides. Furthermore,
this oxidative bromination system is applicable to the
oxidative bromination of alkynes, arenes, and 3,4-
4
2
O
2
dihydronaphthalen-1(2H)-one.
A
gram-scale brominaton
4
). This oxidative bromination reaction proceeded smoothly
reaction was also performed successfully.
in 5 h (Entry 5) although a shorter reaction time caused a
decrease in yield (Entries 6 and 7).
Keywords: Oxidative bromination | Metal-free | Aqueous media
The bromination of organic compounds is regarded as
one of the important reactions in organic synthesis, providing
key precursors for various transformation reactions. Toxic and
hazardous elemental bromine is utilized in conventional
bromination reaction. In this context, oxidative bromination
reaction by using a bromide ion as a bromide source instead
of bromine has attracted much attention, in which a
bromonium cation-like species is generated as
intermediate by two-electron oxidation of a bromide ion. In
these systems, a stoichiometric amount of a potentially
a key
1
hazardous oxidant is required. From
environmentally benign, molecular oxygen and hydrogen
peroxide (H ) are preferred as non-toxic oxidants. Recently,
a viewpoint of
2
O
2
we have already demonstrated the vanadium-catalyzed
oxidative bromination reactions with molecular oxygen to
2
provide the more advanced catalytic systems rather than the
3
enzyme, vanadium bromoperoxidase (VBrPO), which
catalyzes two-electron oxidation of the bromide ion in the
presence of hydrogen peroxide. By using this vanadium-
catalyzed oxidative system, catalytic chlorination and
4
iodination of ketones have been also performed. A transition
metal-free bromination system is considered to be
a
convenient approach for development of environmentally
friendly protocols. The bromination reaction with
5
6
DMSO/HBr and H
2
O /HBr systems as transition metal-free
2
bromination systems have been reported. More
environmentally friendly methodologies under mild
conditions are to be developed. Trifluoroacetic acid (TFA) is
less acidic than HBr. The utilization of trifluoroacetic acid as
an acid is envisioned to be one strategy for the development
of environmentally acceptable oxidative bromination systems
under mild conditions. Hydrogen peroxide is regarded as a
green oxidant because water is the only by-product in
oxidation reactions. Tetrabutylammonium bromide (Bu NBr),
4
which is a quaternary ammonium salt with a bromide ion, is
known to serve as a phase transfer catalyst. From the
viewpoint of green chemistry, we herein report the metal-free
oxidative bromination reactions in aqueous media by using
Bu
4
NBr as a bromide source, TFA as an acid, and H
2
2
O as an
oxidant under mild conditions.

2
The effect of bromide sources was investigated (Table 2).
The use of LiBr or KBr instead of Bu NBr exhibited nearly
0% drop in yield (Entries 2 and 3). The combination of
Table 5 Bromination reactions of phenols in water by using
a
4
Bu NBr/TFA/H O system.
4
2
2
3
Bu4NBr 100 mol%
Bu
4
NBr and LiBr showed good results although a slight
TFA
H2O2
300 mol%
200 mol%
decrease in yield was observed (Entries 4 and 5). Among the
various conditions examined, the reaction with Bu NBr (300
mol%), TFA (300 mol%), and H (300 mol%) in an
Ar
H
Ar Br
4
H2O, Ar, 25 C, 24 h
2
O
2
Product
NMR yield
ultrapure water at 25 °C for 5 h was superior.
Entry
1
Substrate
OMe
OMe
OMe
Br
Br
Br
MeO
OMe
MeO
OMe MeO
OMe
7a, 89%
7b, 2%
OH
OH
2
Br
8
, 72%
a
Reactions conditions: 0.25 mmol of substrate, 0.25 mmol of
bromide source, 0.75 mmol of TFA, 0.5 mmol of H O , 0.5 mL
2
2
°
water, under Ar at 25 C.
To explore the validity of this Bu
4
NBr/TFA/H
2
O
2
bromination system, the reaction of other substrates was
surveyed. The bromination reaction of (2E)-3-phenyl-2-
propen-1-ol resulted in the formation of 38% of the dibromide
2a and 48% of the bromohydrin 2b regioselectively (Table 3,
Entry 1). Allylbenzene underwent the bromination reaction in
an ultrapure water and dichloromethane to give the
corresponding vic-dibromide 3 in 88% yield (Entry 2). 5-
Hexene-1-ol was converted into the dibromide 4 in 70% yield,
with the hydroxy group intact (Entry 3).
The present bromination system could be applied to the
bromination of alkynes (Table 4). The bromination reaction of
1
-phenylpropyne proceeded well to afford the corresponding
trans-1,2-dibromoalkene 5 in 86% yield (Entry 1). The trans-
1
1
,2-dibromoalkene 6 was also obtained in 75% yield from
,4-dimethoxy-2-butyne although a longer reaction time was
Table 4 Bromination reactions of alkynes in water by using
a
required (Entry 2).
The bromination reaction of 1,3,5-trimethoxybenzene
Bu NBr/TFA/H O system.
4
2 2
Bu4NBr 300 mol%
was found to yield the monobromaide 7a and the dibromide
7b in 89% and 2% yields, respectively (Table 5, Entry 1). The
monobromination product 8 could be obtained in 72% yield
by the bromination reaction of 2,6-dimethylphenol (Entry 2).
The -bromination of ketone was also performed. 3,4-
Dihydronaphthalen-1(2H)-one was brominated in the
TFA
H2O2
300 mol%
300 mol%
Br
R2
Br
R1
R2
°
H2O, Ar, 25 C, 5 h
R1
Product
NMR yield
Entry
1
Substrate
presence of 110 mol% Bu
mol% H to allow the formation of the -bromination
product 9 in 76% yield (Scheme 1).
4
NBr, 110 mol% TFA, and 200
Br
2
O
2
Br
5
, 86%
OMe
Br
OMe
2
MeO
MeO
Br
, 75%b
6
a
Reactions conditions: 0.25 mmol of substrate, 0.75 mmol of
bromide source, 0.75 mmol of TFA, 0.75 mmol of H O , 0.5
2
2
°
b
mL water, under Ar at 25 C. Reaction time: 24 h.

3
Wang, X. Li, J.-W. Guo, B. Wang, Tetrahedron Lett. 2014, 55,
058.
It is noteworthy to mention that a gram-scale practical
5
reaction was successfully carried out to give the bromination
product, as exemplified by the bromination of 1-decene to the
dibromide in 74% isolated yield (Scheme 2).
Bu4NBr 200 mol%
TFA
H2O2
300 mol%
300 mol%
Br
Br
7
7
H2O, Ar, 25 C, 5 h
1
.05 g
1, 1.67 g
4% (isolated yield)
7
Scheme 2 Gram-scale bromination reaction of 1-decene in water
by using Bu4NBr/TFA/H2O2 system.
In conclusion, a combination of tetrabutylammonium
bromide as a bromide source, trifluoroacetic acid as an acid,
and hydrogen peroxide as an oxidant has been demonstrated
to induce metal-free oxidative bromination reactions in
aqueous media under mild conditions. This oxidative
bromination system could be applied to the oxidative
bromination of alkenes, alkynes, arenes, and 3,4-
dihydronaphthalen-1(2H)-one.
A
gram-scale brominaton
reaction was also performed successfully. Future work will
concentrate on synthetic versatility and application of this
practical method to other reactions.
This work was supported partly by the ACT-C program
of Japan Science and Technology Agency (JST). Thanks are
due to the Analytical Center, Graduate School of Engineering,
Osaka University.
Supporting Information is available on http://dx.doi.org/.
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