PAPER
Bromination of Alkenes, Alkynes, and Aromatic Amines
3673
Table 1 Influence of the Amount of H5IO6 on the Bromination of
N-Phenylmorpholinea
H5IO6 reagent system that is readily available, inexpen-
sive, and non-toxic. The use of toxic, pure molecular bro-
mine can thus be avoided since it appears only as
intermediate in this reaction.
Entry
H5IO6 (mmol)
Yield (%)b
1
2
3
4
5
0.4
0.6
0.8
1.0
1.2
40
60
65
80
90
Bromination of N-Phenylmorpholine; Typical Procedure
To a solution of N-phenylmorpholine (1.0 mmol, 163 mg) in
CH2Cl2 (5 mL), was added KBr (1.2 mmol, 142 mg) and a solution
of H5IO6 (1.2 mmol, 273 mg) in H2O (5 mL) at r.t. and the mixture
was stirred vigorously at r.t. for 40 min. After completion of the re-
action (indicated by TLC), the reaction mixture was transferred to a
separating funnel and aq Na2S2O3 (10%, 25 mL) was added. The
aqueous fraction was extracted with CH2Cl2 (3 × 15 mL), and the
organic extract was dried with Na2SO4. The solvent was removed
by simple distillation to give the crude product (237 mg; 98%). Fur-
ther purification was carried out by crystallization from cold n-hex-
ane to afford a pale-yellow crystalline product (227 mg, 92%; mp
110–112 °C), which showed satisfactory analytical and spectro-
scopic properties.
a Reaction conditions: KBr (1.2 mmol), 40 min, r.t., CH2Cl2–H2O
(1:1).
b Isolated yield.
Table 2 Comparison of Solvents for Bromination of N-phenylmor-
pholinea
Entry
Solvent
Time (min)
120
Yield (%)b
Bromination of Benzylideneacetone; Typical Procedure
To a solution of benzylideneacetone (1.0 mmol, 146 mg) in CH2Cl2
(5 mL), was added KBr (2.2 mmol, 262 mg) and a solution of H5IO6
(2.3 mmol, 524 mg) in H2O (5 mL) at r.t., and the mixture was
stirred. After completion of the reaction (indicated by TLC), the re-
action mixture was transferred to a separating funnel and aq
Na2S2O3 (10%, 25 mL) was added. The aqueous fraction was ex-
tracted with CH2Cl2 (3 × 15 mL) and the organic layer was dried
with Na2SO4. The solvent was removed by simple distillation to
give the crude product (285 mg, 93%). Further purification was car-
ried out by crystallization (CH2Cl2–n-hexane) to afford a colorless
crystalline product (272 mg, 89%; mp 151–153 °C), which showed
satisfactory analytical and spectroscopic properties.
1
2
3
4
5
6
7
CH2Cl2
–
CH2Cl2/H2O
MeCN
40
90
30
70
80
70
–
120
MeCN–H2O
AcOH
120
180
THF–H2O
n-Hexane
120
120
a Reaction conditions: Substrate (1 mmol), H5IO6 (1.2 mmol), KBr
(1.2 mmol), r.t.
Acknowledgment
b Isolated yield.
The authors acknowledge the Bu-Ali Sina University Research
Council (Grant Number 32-1716), the Center of Excellence in De-
velopment of Chemical Methods (CEDCM) and the National Foun-
dation of Elites (BMN) for support of this work.
Encouraged by these results, various aromatic amines
were subjected to bromination by this method and the re-
sults are collected in Table 3. As can be seen, yields are
good to high and only mono-bromo products were ob-
tained. Other unactivated aromatic compounds such as
benzonitrile and aromatic ketones did not react, and phe-
nolic substrates gave a sluggish reaction.
References
(1) House, H. O. In Modern Synthetic Reactions; W. A.
Benjamin Inc.: Menlo Park, CA, 1972, 422.
(2) Liu, Y. H.; Zhou, S. L. Org. Lett. 2005, 7, 4609.
(3) Johnsson, R.; Meijer, A.; Ellervik, U. Tetrahedron 2005, 61,
11657.
In order to extend the application of this method to other
organic reactions and transformations, we also studied the
bromination of several alkenes with H5IO6/KBr in dichlo-
romethane–water. Bromination of alkenes by this method
took place in very short times and led to trans-configured
1,2-dibromo-compounds which were characterized by
spectroscopic data (Table 4).
(4) Ranu, B. C.; Guchhait, S. K.; Sarkar, A. Chem. Commun.
1998, 2113.
(5) Rieke, R. D.; Sell, M. S. In Handbook of Grignard Reagents;
Silverman, G. S.; Rakita, P. E. M., Eds.; Dekker: New York,
1996, 527.
(6) Normant, H. Adv. Org. Chem. 1960, 2, 1.
(7) Wakefield, B. J. The Chemistry of Organolithium
Compounds; Pergamon Press: Oxford, 1976.
(8) Davis, S. G. Organotransition Metal Chemistry:
Applications to Organic Synthesis; Pergamon Press: Oxford,
1982.
The reaction pathway probably involves oxidation of the
bromide ion to an electrophilic bromine molecule, which
then reacts with the alkene to form a cyclic bromonium
ion intermediate. The latter is then attacked by a bromide
ion from the reverse side, selectively forming the trans-
vicinal dibromo compound.
(9) Cannon, K. C.; Krow, G. R. Handbook of Grignard
Reagents; Dekker: New York, 1996.
(10) Still, J. K. Pure Appl. Chem. 1985, 57, 1771.
(11) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(12) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100,
3009.
In conclusion, we have developed a very simple, mild,
novel, and efficient method for high-yielding bromination
of alkenes, alkynes, and aromatic amines, using a KBr/
Synthesis 2009, No. 21, 3672–3676 © Thieme Stuttgart · New York