Electrophilic bromination of alkenes, alkynes, and aromatic amines with iodic acid/potassium bromide under mild conditions

Article abstract of DOI:10.1080/00397910903349992

Bromination of alkenes, alkynes, and aromatic amines has efficiently been carried out at room temperature in short reaction times using HIO ₃/KBr in CH₂Cl₂/H₂O (1:1) to prepare corresponding brominated compounds in excellent yields.

Full text of DOI:10.1080/00397910903349992

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Electrophilic Bromination of Alkenes,
Alkynes, and Aromatic Amines with Iodic
Acid/Potassium Bromide Under Mild
Conditions
Ardeshir Khazaei a , Mohammad Ali Zolfigol a , Eskandar Kolvari b
Nadiya Koukabi a , Hamid Soltani a & Leyla Sharaf Bayani a
a Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
,
b Department of Chemistry, Faculty of Science, Semnan University,
Semnan, Iran
Version of record first published: 25 Aug 2010.
To cite this article: Ardeshir Khazaei, Mohammad Ali Zolfigol, Eskandar Kolvari, Nadiya Koukabi,
Hamid Soltani & Leyla Sharaf Bayani (2010): Electrophilic Bromination of Alkenes, Alkynes,
and Aromatic Amines with Iodic Acid/Potassium Bromide Under Mild Conditions, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
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Synthetic Communications1, 40: 2954–2962, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903349992
ELECTROPHILIC BROMINATION OF ALKENES,
ALKYNES, AND AROMATIC AMINES WITH IODIC ACID/
POTASSIUM BROMIDE UNDER MILD CONDITIONS
Ardeshir Khazaei,1 Mohammad Ali Zolfigol,1
Eskandar Kolvari,2 Nadiya Koukabi,1 Hamid Soltani,1 and
Leyla Sharaf Bayani1
1Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
2Department of Chemistry, Faculty of Science, Semnan University,
Semnan, Iran
Bromination of alkenes, alkynes, and aromatic amines has efficiently been carried out at
room temperature in short reaction times using HIO3/KBr in CH2Cl2/H2O (1:1) to prepare
corresponding brominated compounds in excellent yields.
Keywords: Alkenes; alkynes; aromatic amines; bromination; iodic acid
INTRODUCTION
Organic halides are an important class of intermediates because they can be
converted efficiently into other compounds by simple chemical transformations.[1–3]
The protection and deprotection of double bonds via a bromination–debromina-
tion strategy is finding increasing applications in organic synthesis.[4] Addition-
ally, the brominated alkenes and arenes are useful precursors to organometallic
reagents[5–8] and play vital roles in transition metal–mediated coupling
reactions.[9–12]
These compounds have much considerable commercial importance such as
potent antitumor, antibacterial, antifungal, antineoplastic, antiviral, and antioxidizing
agents.[13,14] In addition, several industrial intermediates for the manufacture of
speciality chemicals, pharmaceuticals, agrochemicals, medicinally active molecules,
fire retardants, and other newer materials bear halogen functionality.
Conventional halogenation methods[15–19] typically use elemental halogens
(X2), which are dangerous pollutants and generate hazardous hydrohalic
acids as by-products. The generated hydrohalic acid waste in the halogenations
of aromatic compounds effectively reduces atom efficiency by 50% and must be
Received August 22, 2009.
Address correspondence to Ardeshir Khazaei and Mohammed Ali Zolfigol, Faculty of Chemistry,
Bu-Ali Sina University, Hamedan, Iran. E-mails: khazaei_1326@yahoo.com; zolfi@basu.ac.ir and
Eskandar Kolvari, Department of Chemistry, Faculty of Science, Semnan University, Semnan, Iran.
E-mail: kolvari@semnan.ac.ir
2954

BROMINATION BY HIO3/KBr
2955
neutralized before it can be discharged as effluent. To avoid the use of molecular
halogens, the development of environmentally friendly halogenation has been
focused on.[20–26]
Recently, the oxidative halogenation of organic compounds by metal
halides has emerged as an important alternative for the synthesis of such bromo
compounds.[27–32]
Despite the broad choice of options,[25,33–36] many brominating methodolo-
gies are cumbersome, costly, and harsh or involve use of toxic heavy metals or
elemental bromine. The development of quick, inexpensive, widely applicable,
and environmentally benign brominating agents is therefore still an active area
of research.
RESULTS AND DISCUSSION
Iodic acid (HIO3) has attracted much interest owing to its potential as an
oxidant.[37–42] The use of iodic acid has been known for a long time and has
been widely employed in numerous organic reactions such as iodination[38,43] and
deprotection.[44]
This reagent has several advantages: cost-effectiveness, low toxicity to humans,
and the exceedingly simple and clean workup of products.
In continuation of our work[42] on the development of useful synthetic
methodologies, we observed that potassium bromide in the presence of iodic acid
(HIO3) is an effective reagent system for bromination of alkenes, alkynes, and
aromatic amines (Scheme 1).
Our studies were initiated by treatment of N-phenylmorpholine with potassium
bromide and iodic acid in a two-phase system consisting of H2O and CH2Cl2. A facile
reaction occurred, and the 4-(4-bromophenyl)morpholine was isolated in 92% yield.
Concomitant tests were carried out to optimize reaction conditions with respect to
the oxidant and solvent. Tables 1 and 2 summarize the results. As can be seen from
these two tables, CH2Cl2=H2O (1:1) as a two-phase system and HIO3 (1.2 mmol) are
the best overall.
Scheme 1. Bromination of alkenes and aromatic amines using KBr and iodic acid.

2956
A. KHAZAEI ET AL.
Table 1. Influence of HIO3 amount on the bromination yield
of N-phenymorpholinea
Entry
HIO3 (mmol)
Yield (%)b
1
2
3
4
5
6
0.4
0.6
0.8
1
40
60
68
80
92
92
1.2
1.4
aReaction conditions: KBr (1.2 mmol), time: 40 min, solvent:
CH2Cl2=H2O (1:1), room temperature.
bIsolated yields.
Encouraged by these results, we subjected different aromatic amines to bro-
mination by this method. Results are collected in Table 3. As can be seen, yields
are good to excellent, and selective mono bromo products have been obtained. Other
unactivated aromatic compounds such as benzonitrile and aromatic ketones did not
react, and phenolic substrates gave sluggish reactions. Even though HIO3=KBr is
capable of oxidizing alcohol,[42] it remains intact during the iodination of aromatic
nucleus (entry 4).
To extend the application of this method in organic reactions and trans-
formations, we have also studied bromination of several alkenes with HIO3=KBr
in CH2Cl2=H2O as solvent. Bromination of alkenes by this method took place in
very short times and led to trans-configured 1,2-dibromo compounds, which were
analyzed by analytical procedures (1H NMR and 13C NMR) (Table 4).
The reaction pathway consists of oxidation of a bromide ion to an elec-
trophilic bromine molecule, which is responsible for reacting with the alkene
to form a cyclic bromonium ion intermediate, which then is attacked by a
bromide ion from the reverse side, forming a selectively trans-vicinal 1,2-dibromo
compound.
Table 2. Comparison of different solvents for bromination of N-phenylmorpholine
(1.0 mmol) using HIO3 (1.2 mmol) and KBr (1.2 mmol)
Entry
Solvent
Time (min)
Yield (%)a
1
2
3
4
5
6
7
9
CH2Cl2
CH2Cl2=H2O
CH3CN
180
40
—
92
20
60
88
75
—
—
120
120
180
120
120
120
CH3CN=H2O
CH3CH2OH
THF=H2O
CHCl3
n-Hexane
aRefers to isolated yields.

BROMINATION BY HIO3/KBr
2957
Table 3. Bromination of aromatic amines to mono bromo derivatives with HIO3 in the presence of KBr
in CH2Cl2 and H2O (1:1) at room temperature
Time
(min)
Yield
(%)a
Entry
1
Substrate
Product
Ref.
34
10
7
90
80
92
2
3
35
35
40
4
5
15
45
79
70
35
35
6
7
20
95
90
35
38
5
—
8
9
120
120
15
—
—
—
—
—
—
—
10
Sluggish
aRefers to isolated yields.

2958
A. KHAZAEI ET AL.
Table 4. Bromination of alkenes and alkynes to their corresponding bromominated compounds with
HIO3 in the presence of KBr in CH2Cl2 and H2O (1:1) at room temperature
Entry
1
Substrate
Product
Time (min)
15
Yield (%)a
Ref.
—
80
2
3
10
10
89
99
32
33
4
5
6
10
10
10
86
86
99
32
—
—
7
8
10
9
81
80
30
37
9
15
20
83
—
36
10
87b
11
15
94
30
aRefers to isolated yields.
bReaction condition: HIO3 (4.8 mmol), KBr (4.4 mmol), and phenylacetylene (1.0 mmol).

BROMINATION BY HIO3/KBr
2959
EXPERIMENTAL
Typical Procedure for the Bromination of N-Phenylmorpholine
KBr (1.2 mmol, 140 mg) and a solution of HIO3 (1.2 mmol, 211 mg) in H2O
(5 mL) were added to a mixture of N-phenylmorpholine (1.0 mmol, 163 mg) in
CH2Cl2 (5 mL) at room temperature, and the mixture was stirred vigorously
for 40 min at room temperature. After thin-layer chromatography (TLC) indi-
cated completion of the reaction, the reaction mixture was transferred to a
separatory funnel and a 10% aqueous Na2S2O3 solution (25 mL) was added.
The aqueous fraction was extracted with CH2Cl2 (3 Â 15 mL). The organic layer
was dried with Na2SO4. The solvent was removed by simple distillation to give a
crude product (237 mg; 98%). Further purification was carried out by crystalliza-
tion from cold n-hexane to afford a pale yellow crystalline product (226 mg; 92%)
with mp 110–112 ꢀC, which showed satisfactory analytical and spectroscopic
properties.
Typical Procedure for the Bromination of Benzylideneacetone
KBr (2.2 mmol, 262 mg) and a solution of HIO3 (2.4 mmol, 422 mg) in H2O
(5 mL) were added to a solution of benzyldeneacetone (1.0 mmol, 146 mg)
in CH2Cl2 (5 mL) at room temperature and stirred. After completion of the reac-
tion, indicated by TLC, the reaction mixture was transferred to a separatory
funnel, and a 10% aqueous Na2S2O3 solution (25 mL) was added to it. The aque-
ous fraction was extracted with CH2Cl2 (3 Â 15 mL). The organic layer was
dried with Na2SO4. The solvent was removed by simple distillation to give a
crude product (283 mg, 93%). Further purification was carried out by crystalliza-
tion from CH2Cl2=n-hexane to afford a colorless crystalline product (271 mg;
89%), with mp 122–124 ꢀC, which showed satisfactory analytical and spectro-
scopic properties.
CONCLUSION
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=HIO3 system, which is readily available, inexpensive, and nontoxic.
Pure molecular bromine, which is toxic, can thus be avoided; it appears only as an
intermediate in this reaction.
ACKNOWLEDGMENTS
The authors acknowledge the Bu-Ali Sina University Research Council
(Grant Number 32-1716), the Center of Excellence in Development of Chemical
Methods (CEDCM), and the National Foundation of Elites (BMN) for support
of this work.

2960
A. KHAZAEI ET AL.
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