A convenient and useful method of preparation of α-bromo enones from the corresponding enones using organic ammonium tribromide (OATB)

Article abstract of DOI:10.1246/cl.2001.290

Various acyclic α-bromo enones 2 as well as cyclic α-bromo enones 4 can be prepared from the corresponding acyclic enones 1 and cyclic enones 3 respectively, in a one-pot procedure by employing organic ammonium tribromide, such as cetyltrimethylammonium t

Full text of DOI:10.1246/cl.2001.290

290
Chemistry Letters 2001
A Convenient and Useful Method of Preparation of α-Bromo Enones from the Corresponding
Enones Using Organic Ammonium Tribromide (OATB)1
Gopal Bose, Pankaj M. Bujar Barua, Mihir K. Chaudhuri, Dipak Kalita, and Abu T. Khan*
Department of Chemistry, Indian Institute of Technology, Guwahati 781039, Assam, India
(Received December 19; CL-001140)
Various acyclic α-bromo enones 2 as well as cyclic α-
bromo enones 4 can be prepared from the corresponding acyclic
enones 1 and cyclic enones 3 respectively, in a one-pot proce-
dure by employing organic ammonium tribromide, such as
cetyltrimethylammonium tribromide (CetTMATB) or
tetrabutylammonium tribromide (TBATB) in presence of
K2CO3 in dichloromethane at 0 °C to room temperature under
very mild conditions in good yields.2
compound 1a using TBATB in similar solvent system (Method
B) at 0 °C–rt (Scheme 1 ). It may be noted that no bromination
took place at C-1 position of 1a. The E/Z ratio is ascertained by
GC and 1H NMR. Likewise, the reaction of 4-(4-
methoxyphenyl)-3-buten-2-one (1b) with CetTMATB or
TBATB, under exactly similar reaction conditions afforded 3-
bromo-4-(4-methoxyphenyl)-3-buten-2-one (2b) as E/Z mixture
(Scheme 1). When R1 is phenyl present in the substrate then
base K2CO3 is usually added after 3.5 h, otherwise it is added
after 45 min exactly. Similarly, the substrates 1c, 1d, 1e, and 1f
are sucessfully converted into the corresponding α -bro-
moenones 2c, 2d, 2e, and 2f respectively at 0 °C to room tem-
perature (Table 1). Also, the reaction of an α,β-unsaturated
ester, viz., methyl cinnamate 1g, with CetTMATB or TBATB
followed by treatment with K2CO3, provided α-bromo-α,β−
unsaturated ester 2g. α-Bromo-α,β−unsaturated esters are usu-
ally prepared11 via arsonium ylides.
The preparation of α-bromo enone has some considerable
interest to the synthetic chemist for natural3 and non-natural
product4 synthesis. It also serves as an essential precursor for
generating α-keto vinyl anion equivalent for further use in
organic synthesis.5 For instance, α-bromo cyclopentenone (4a)
has been used for the preparation of α-hydroxymethylcyclopen-
tenone, which is a valuable starting material for natural prod-
ucts synthesis.6 In addition, some of the α-bromo enones are
also found in nature.7 Although the preparation of these com-
pounds are well known in literature,8 still there is a need to find
out much milder and better alternatives. The existing methods8
are available so far i) bromination of enones with elemental
bromine followed by dehydrobromination, using a suitable base
such as triethylamine3a,5 or sodium hydrogencarbonate3b; ii)
reaction of enones with excess phenylselenium bromide, fol-
lowed by treatment with a base pyridine8c; iii) epoxidation of
enones using dimethyldioxirane, followed by epoxide ring
opening with alkali metal bromide such as sodium bromide, and
consequent dehydration.8d All these present methods have
some drawbacks, such as molecular bromine is hazardous, diffi-
cult to maintain stiochiometric ratio and difficult to handle. On
the other hand, the reagent phenylselenium bromide is toxic,
expensive, and it also requires much longer reaction time to
obtain the product. Sometimes it is failed to obtain β-substitut-
ed cyclic α -bromo enones by using elemental bromine.8b
Therefore, a clean preparation of α-bromo enone is highly
desirable. In an endeavour to change gradually the current
working practices with greener alternatives, an enviroumentally
favorable synthesis of organic ammonium tribromides (OATB),
and some of its application is recently disclosed.9 In the course
of these studies, our attention is drawn to the problems of
bromination of enones as highlighted above. Due to potentiali-
ty of organic ammonium tribromide (OATB) as a brominating
agent,10 it is expected to be possible to get an easy access to α-
bromo enones from the bromination of enones with this type of
reagents. The results of our successful attempts are reported in
this communication. Thus, the reaction of trans-4-phenyl-3-
buten-2-one (1a) with CetTMATB in CH2Cl2 at 0–5 °C, fol-
lowed by treatment with K2CO3 at room temp gave E/Z (28/72)
mixture of 3-bromo-4-phenyl-3-buten-2-one (2a) in a very good
yield (Method A). The compound 2a is also prepared from
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
291
Similarly, various cyclic enones (3a–e) reacted12 with
CetTMATB or TBATB in presence of K2CO3 at 0 °C–rt to pro-
vide readily the cyclic α-bromo enones (4a–e) in good yields
(Scheme 2, Table 2). The generation of α-bromo enones can be
explained by the initial formation of dibromo ketones, followed
by readily dehydrobromination by a base such as K2CO3.
The authors are thankful for the financial support from
Council of Scientific and Industrial Research, New Delhi
[Grant No. 01(1541)/98/EMR-II to A.T.K] and the referees
valuable comments.
References and Notes
1
2
3
4
5
6
7
This paper is dedicated to Professor Richard R. Schmidt,
Universitaet Konstanz, Germany on the occasion of his
65th birthday.
This work was presented by A. T. Khan at the 13th
International Conference on Organic Synthesis at Warsaw
in Poland, July 1–5, 2000.
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Org. Chem., 33, 1454 (1968). b) S. Arai, K. Nakayama, T.
Ishida, and T. Shioiri, Tetrahedron Lett., 40, 4215 (1999).
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A. B. Smith, III, in “Strategies and Tactics in Organic
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G. W. Gribble, in “Progress in the Chemisty of Organic
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Vienna (1996), pp. 17–22 and references cited therein.
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M. K. Chaudnuri, A. T. Khan, B. K. Patel, D. Dey, W.
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12 Method A: To a stirred solution of 2-cyclopenten-l-one
(3a) (0.410 g, 5 mmol) in CH2Cl2 (10 mL) are added
cetyltrimethylammonium tribromide (2.62 g, 5 mmol) and
K2CO3 (2.07 g, 15 mmol) at 0–5 °C. Stirring is continued
for 20 min at the same temperature, and then it is brought
slowly to room temperature. The reaction is completed
within 40 min as monitored by TLC. Then, the white solid
is filtered off and the solid residue was washed with 10 mL
of dichloromethane. The combined filtrate is concentrated
in rotavapor and the crude product is purified by chro-
matography on silica gel (60–120 mesh). The compound is
eluted with ethyl acetate–hexane mixture(1:9) and the
product 4a is obtained as a gummy liquid in 70 % yield
(0.564 g). Method B: The compound 4a is also prepared
from 3a using TBATB at 0–5 °C following the identical
procedure as above.
In conclusion, we have devised a simple and useful method
for the synthesis of α-bromo enones from enones by employing
organic ammonium tribromide, such as cetyltrimethylammoni-
um tribromide or tetrabutylammonium tribromide as brominat-
ing agent under mild and environmentally favorable conditions.
In addition, we have also achieved the preparation of β-substi-
tuted cyclic α-bromo enones. Owing to its operational simplic-
ity, generality and efficacy, this method is expected to have
wide utility for the synthesis of α-bromo enones. A similar
transformation might be possible also with other organic
ammonium tribromides, which is under investigation.