Organic Process Research & Development 1999, 3, 5−9
Articles
A Process Scheme Involving Transalkylation Reactions To Prepare
o-Bromophenol from Phenol
Nikhil R. Trivedi and Sampatraj B. Chandalia*
Department of Chemical Technology, UniVersity of Mumbai, Matunga, Mumbai-400 019, India
Abstract:
be transferred to another aromatic ring via a transalkylation
The bromination of phenol to o-bromophenol was carried out
by protecting the para position with a tert-butyl group. The
latter group was subsequently transferred to toluene using
aluminum chloride as a catalyst. The resulting mixture of p-
and m-tert-butyltoluene could be converted back to p-tert-
butylphenol by transalkylation of the former with phenol in
the presence of Engelhard, F-24. Thus, a process scheme based
on transalkylation reactions as the intermediate steps has been
proposed to synthesize o-bromophenol from phenol via p-tert-
butylphenol. The effect of reaction parameters on overall
conversion to and selectivity with respect to the desired product
was studied for the transalkylation reactions involved in the
process.
reaction. Tashiro et al.4 have reported the use of tert-butyl
and benzyl groups as protecting groups in ortho-chlorination
and -bromination of phenol. They have obtained o-bro-
mophenol (OBP) in 82% yield by transalkylation of o-bromo-
p-tert-butylphenol (OBPTBP) using benzene as an alkyl
group acceptor and AlCl3-CH3NO2 as a catalyst. This work
was, therefore, carried out on similar lines to investigate the
possibility of using toluene instead of benzene as an alkyl
group acceptor and aluminum chloride as catalyst. The
resulting mixture of p- and m-tert-butyltoluene (PTBT and
MTBT) was used for obtaining p-tert-butylphenol (PTBP)
by a transalkylation reaction with phenol in the presence of
Engelhard, F-24. In this process, the amount of waste
products is minimized, although the number of steps used
in the process increases. Thus, a process scheme involving
transalkylation reactions to prepare o-bromophenol from
phenol via p-tert-butylphenol was developed, which consists
of three reactions as shown in Figure 1.
1. Introduction
o-Halogenated phenols are important intermediates for the
synthesis of catechol and its derivatives, which have diverse
uses in the preparation of pharmaceuticals, agrochemical,
flavors, antioxidants, and polymer inhibitors. However, the
halogenation of phenols at room temperature invariably gives
a mixture of ortho and para isomers, para isomers being
the major product. Pearson et al.1 have brominated phenols
exclusively at the ortho position in the presence of tert-
butylamine or triethylenediamine; however, the reaction was
carried out at a very low temperature of about -70 °C.
Hence, a general approach to obtain o-bromophenol in good
yield is by an indirect procedure, involving blocking of the
para position of phenol with a subsistent which can later be
removed. Patai and Rapport2 have summerized indirect
procedures for obtaining o-halophenols, in which the para
position is protected by carboxylic acid, sulfonic acid, and
amino groups. However, as reported by Francis and Hill,3
groups such as carboxylic acid and sulfonic acid are likely
to be partially replaced by bromine during the bromination
step. This problem can be circumvented by protecting the
para position with a tert-butyl group, which is fairly stable
under the conditions employed during bromination and can
2. Experimental Section
All the materials used were of technical grade. The clay
catalyst Engelhard, F-24, was obtained from Engelhard, Corp.
(Iselin, NJ). The experiments were carried out in a 0.5-L
capacity glass reactor, provided with a six-blade turbine
stirrer, four baffles, and a thermometer pocket. The reactor
was placed in a constant-temperature bath.
2.1. Monobromination of PTBP. PTBP (2 mol/L) in
1,2-dichloroethane was taken in a reactor, and liquid bromine
(2.1 mol/L) was added to it in 3 h by a dropping funnel.
The reaction was carried out at 30 °C with continuous
stirring. A slight excess of bromine was added to compen-
sate for the loss due to vaporization. After complete addition
of bromine, the reaction mixture was stirred for 1 h, and the
product mixture was extracted with water to remove dis-
solved hydrogen bromide. The organic layer was dried over
anhydrous sodium sulfate and solvent distilled to give
OBPTBP in 98% yield.
2.2. Transalkylation of OBPTBP. Predetermined quan-
tities of toluene, OBPTBP, and anhydrous aluminum chloride
were taken in the reactor and stirred at the desired temper-
ature. After the predetermined reaction period was over, the
(1) Pearson, D. E.; Wysong, R. D.; Breder, C. V. J.; J. Org. Chem. 1967, 32,
2358-60.
(2) Patai, S.; Rapport, A. The chemistry of functional groups; Wiley: New York,
1983; Supplement D, Part 1, pp 522-32.
(3) Francis, A. W.; Hill, A. J. J. Am. Chem. Soc. 1924, 46, 2498-505.
(4) Tashiro M.; Watanabe, H.; Tsuge, O. Org. Prep. Proced. Int. 1974, 6 (3),
107-15.
10.1021/op9800360 CCC: $18.00 © 1999 American Chemical Society and Royal Society of Chemistry
Published on Web 11/20/1998
Vol. 3, No. 1, 1999 / Organic Process Research & Development
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