Regioselective aromatic electrophilic bromination with dioxane dibromide under solvent-free conditions

Article abstract of DOI:10.1080/00397910601055081

Highly regioselective ring bromination of aromatic compounds has been accomplished with high yields and good purity using dioxane dibromide (DD) under solvent-free conditions. Notable features of this methodology include operational simplicity, rapid reactions, excellent control over the degree of bromination, and tolerance of various functional groups during the reaction. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601055081

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Regioselective Aromatic Electrophilic
Bromination with Dioxane Dibromide Under
Solvent‐Free Conditions
Subrata Kumar Chaudhuri a , Sanchita Roy a , M. Saha a & Sanjay Bhar a
a Department of Chemistry, Organic Chemistry Section, Jadavpur University,
Kolkata, India
Published online: 05 Mar 2007.
To cite this article: Subrata Kumar Chaudhuri , Sanchita Roy , M. Saha & Sanjay Bhar (2007) Regioselective
Aromatic Electrophilic Bromination with Dioxane Dibromide Under Solvent‐Free Conditions, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:4,
579-583, DOI: 10.1080/00397910601055081
To link to this article: http://dx.doi.org/10.1080/00397910601055081
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Synthetic Communicationsw, 37: 579–583, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601055081
Regioselective Aromatic Electrophilic
Bromination with Dioxane Dibromide
Under Solvent-Free Conditions
Subrata Kumar Chaudhuri, Sanchita Roy,
M. Saha, and Sanjay Bhar
Department of Chemistry, Organic Chemistry Section,
Jadavpur University, Kolkata, India
Abstract: Highly regioselective ring bromination of aromatic compounds has been
accomplished with high yields and good purity using dioxane dibromide (DD) under
solvent-free conditions. Notable features of this methodology include operational sim-
plicity, rapid reactions, excellent control over the degree of bromination, and tolerance
of various functional groups during the reaction.
Keywords: electrophilic aromatic substitution, regioselectivity, solid-phase synthesis
Ring bromination[1] of aromatic compounds is an important reaction in
organic synthesis. Numerous methods have been developed, which include
the classical use of molecular bromine[2,3] in various organic (mainly haloge-
nated) solvents. To prevent loss due to high volatility, an excess amount of
bromine is often used during the reaction to drive the reaction to completion.
The products of the reactions are generally complicated and contaminated
with by-products[1–3] due to poor regioselectivity, overbromination, and
oxidative and polymeric transformations of the sensitive substrates and
products. Toxicity, corrosive, lachrymatory, and the fuming nature are the
most serious disadvantages of the conventional bromination methods. There
are some reports[4] of alternative bromination procedures, but most of them
Received in India July 10, 2006
Address correspondence to Sanjay Bhar, Department of Chemistry, Organic
Chemistry Section, Jadavpur University, Kolkata 700032, India. E-mail:
sanjaybharin@yahoo.com or sssbhar@lycos.com
579

580
S. K. Chaudhuri et al.
involve drastic reaction conditions, costly reagents, and organic solvents as
reaction media. We report herein a mild, solvent-free protocol using
dioxane dibromide (DD) for highly regioselective aromatic electrophilic bro-
mination (Scheme 1); the results are furnished in Table 1.
As is evident from Table 1, the compounds underwent clean and
regioselective ring bromination with good yields and high purity within a
reasonable period of time. A notable feature of the present methodology
was excellent control over the degree of bromination (entries 2, 4–7 in
Table 1) by using duly weighed, calculated amounts of DD. This was rarely
observed in the most of the earlier reports. Phenol (entry 5) and anisole
(entry 7) were not overbrominated beyond 2,4-dibromo- derivatives despite
the use of an excess amount of DD. So, the present method can serve as an
efficient and relatively green protocol for the single-step preparation of com-
mercially important 2,4-dibromoaromatics from easily accessible precursors.
Sensitive moieties, such as methoxycarbonyl (entries 8, 9) and formyl (entries
10, 11), were also tolerant of this method. 3-Hydroxybenzaldehyde has been
reported[3b] to yield regioisomeric monobrominated products in various pro-
portions when molecular bromine in different organic solvents is used as
the brominating agent, but in the present method, 6-bromo-3-hydroxybenzal-
dehyde was obtained almost exclusively in high yield (entry 11) with minimal
formation of isomeric by-products (by 300-MHz 1H NMR). The more
electron-rich aromatic ring underwent preferential bromination in phenyl
benzoate (entry 12), which on hydrolysis led to the exclusive formation of
4-bromophenol. Bromination of 2-aminobenzoic acid led to 2-amino-3,5-
dibromobenzoic acid and 2,4,6-tribromoaniline in a 45:55 ratio (determined
by 1H NMR). Treatment of 2-hydroxybenzoic acid with a large excess
amount of DD (greater than 6 equiv) led to the formation of a ternary
mixture of 5-bromo-2-hydroxybenzoic acid, 3,5-dibromo-2-hydroxybenzoic
acid, and 2,4,6-tribromophenol in a 23:61:16 ratio (determined by 1H
NMR). Hydroquinone, which is highly susceptible to oxidative transform-
ations, also underwent clean bromination with DD to yield highly substituted
2,3,5-tribromo-1,4-dihydroxybenzene (characterized by 1H NMR and 13C
NMR of the corresponding acetate) in good yield (73%).
In conclusion, a good preparative method has been developed for syn-
thetically and commercially important functionalized bromoaromatics with
good yield, high purity, and excellent selectivity through operationally simple
and relatively green procedures. Notable advantages of the methodology
Scheme 1.

Regioselective Aromatic Bromination
581
Table 1. Selective bromination of aromatic compounds with dioxane dibromide
under solvent-free conditions
Mol. eqv.
of DD
Time
(min)
Yielda
(%)
Entry
1
Substrate
Product
1.5
1.2
2.5
30
15
30
84[2,5]
75[2,5]
87[2,5]
2
3
4
5
1.2
10
20
61 (70b)[2]
80[2,5]
.4.0
6
7
1.5
15
45
85[2,5]
86[2]
.4.0
8
9
1.5
1.5
1.0
1.1
30
30
30
30
74
85
10
11
82
80[3b]
12
1.5
30
75[2]
aYield refers to that of isolated pure products, characterized chemically and
spectroscopically.
1
bBy H NMR, remainder 2,4-dibromophenol.

582
S. K. Chaudhuri et al.
include 1) excellent control over the degree of bromination, 2) high
regioselectivity, 3) minimization of organic solvents as reaction medium by
carrying out the reactions under solvent-free conditions, 4) tolerance of
sensitive functional groups, and 5) general applicability, accommodating a
variety of substitution patterns.
EXPERIMENTAL
General Procedure for Bromination Using DD
DD (as required by the stoichiometry as in Table 1) was added in portions to
the neat substrate (5 mmol, cooled at 0–58C in ice water) and well mixed. The
mixture was allowed to attain the ambient temperature and left for the stipu-
lated time period (as mentioned in Table 1). Crushed ice was then added to the
reaction mixture and filtered (if the product was solid) or extracted with ether
(for a semisolid or liquid mass), and it was washed successively with saturated
aqueous sodium bicarbonate solution and water and dried to get the product in
almost pure form. The products were further purified by crystallization, short-
path distillation, or filtration chromatography on a short column of silica gel
using 5% ethyl acetate–petroleum ether, if needed.
ACKNOWLEDGMENTS
Financial support from the Council of Industrial and Scientific Research, New
Delhi (Grant No. 01(1673)/00/EMR-II dated 07-12-2000), is gratefully
acknowledged. S. R. thanks the University Grants Commission, New Delhi,
and M. S. thanks CSIR, New Delhi, for junior research fellowships. The
authors express profound thanks to N. Dutta of the Indian Association for
the Cultivation of Science for necessary assistance.
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