Ionic liquid promoted selective debromination of α-bromoketones under microwave irradiation

Article abstract of DOI:10.1016/j.tet.2006.10.035

The debromination of α-bromoketones with an easily accessible ionic liquid, 1-methyl-3-pentylimidazolium tetrafluoroborate, [pmIm]BF₄ under microwave irradiation has been investigated. By controlling the reaction time gem-α-dibromoketones are selectively debrominated to either monobromo or debromoketones. The α-monobromo- and α-monoiodoketones are dehalogenated while the corresponding chloroketones remain inert. The activated vic-bromoacetates are converted to the corresponding (E)-alkenes by the same procedure. These reactions do not require any organic solvent, any metal or any conventional reducing agent. The ionic liquid works here as catalyst as well as reaction medium and is recycled without any appreciable loss of its catalytic efficiency.

Full text of DOI:10.1016/j.tet.2006.10.035

Tetrahedron 63 (2007) 155–159
Ionic liquid promoted selective debromination of a-bromoketones
under microwave irradiation
*
Brindaban C. Ranu, Kalicharan Chattopadhyay and Ranjan Jana
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata—700 032, West Bengal, India
Received 17 July 2006; revised 27 September 2006; accepted 12 October 2006
Available online 9 November 2006
Abstract—The debromination of a-bromoketones with an easily accessible ionic liquid, 1-methyl-3-pentylimidazolium tetrafluoroborate,
[pmIm]BF4 under microwave irradiation has been investigated. By controlling the reaction time gem-a-dibromoketones are selectively
debrominated to either monobromo or debromoketones. The a-monobromo- and a-monoiodoketones are dehalogenated while the corre-
sponding chloroketones remain inert. The activated vic-bromoacetates are converted to the corresponding (E)-alkenes by the same procedure.
These reactions do not require any organic solvent, any metal or any conventional reducing agent. The ionic liquid works here as catalyst as
well as reaction medium and is recycled without any appreciable loss of its catalytic efficiency.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
application of this ionic liquid for selective debromination
of gem-a-dibromoketones to monobromo- and debromo-
ketones by proper control of reaction time (Scheme 1).
The selective debromination of a-bromoketones is a useful
transformation in organic synthesis and remains a challeng-
ing problem because of the presence of more than one reduc-
ible groups.1 The problem becomes more complicated in
a-dibromoketones particularly when selective debromina-
tion of one bromo group is required. Although, a number of
methods have been reported2 for the debromination of a-bro-
mocarbonyl compounds using a variety of reagents2 such as
triphenyl phosphine in methanol,2a pyridinium salts,2b hyd-
ridotetracarbonylferrate anion,2c molybdenum hexacarbonyl
on alumina,2d sodium iodide–chlorotrimethylsilane,2e tri-
phenylphosphonium iodide,2f sodium borohydride–antimony
tribromide,2g sodium amalgam in CH3OD,2h HBr–ACOH–
Na2S2O4,2i n-Bu3SnH,2j zinc in AcOH,2k none of these
procedures addressed monodebromination of gem-a-dibro-
moketones. Our literature search (SciFinder, SCOPUS)
also did not reveal any such method. This prompted us to
find a suitable method for this challenging transformation.
O
O
O
R2
[pmIm]BF4/H2O
MW, 2-3 min
R2
[pmIm]BF4/H2O
5-7 min, MW
R2
R1
R1
R1
Br
Br
Br
R1 = Ar, OEt; R2 = COPh, COMe, Me, H
Scheme 1.
2. Results and discussion
The experimental procedure is very simple. A mixture of
gem-a-dibromoketone and [pmIm]BF4 with a drop of H2O
was heated under microwave (MW) irradiation. The mono-
bromoketone was obtained by irradiation over 2–3 min
(TLC) and the doubly debrominated ketone was isolated by
irradiation for 5–7 min. In each case, the product was isolated
by extraction with ethyl acetate followed by purification by
column chromatography. The remaining ionic liquid after
being washed and dried was reused for five runs without
any appreciable loss of efficacy. After five runs fresh ionic
liquid (half of the initial amount taken) was added and the
reaction was continued without any difficulty.
We have been very actively engaged in exploring new facets
of ionic liquids3 in organic transformations for last few years
and as a part of this program4 we recently developed a simple
procedure for the stereoselective debromination of vic-
dibromides by an easily accessible ionic liquid 1-methyl-
3-pentylimidazolium tetrafluoroborate, [pmIm]BF4 under
microwave irradiation.4j We report here another novel
Several activated gem-a-dibromoketones were reacted
according to this procedure to produce either monobromo-
ketones or doubly debrominated ketone when exposed to
microwave irradiation for a selective period of time. The re-
sults are summarized in Table 1. It was found that the crude
Keywords: Ionic liquid; Bromoketones; Debromination; Microwave irradi-
ation.
* Corresponding author. Tel.: +91 33 2473 4971; fax: +91 33 2473 2805;
e-mail: ocbcr@iacs.res.in
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.10.035

156
B. C. Ranu et al. / Tetrahedron 63 (2007) 155–159
Table 1. Selective debromination of dibromo compounds catalyzed by
[pmIm]BF4
Table 2. Dehalogenation of a-halo ketones and esters catalyzed by
[pmIm]BF4
Entry
Substrate
Time
(min)
Product
Yield Ref.
(%)a
Entry
Substrate
Time
(min)
Product
Yield Ref.
(%)a
O
O
O
O
Br
Br
Br
Br
1
4.0
3.5
4.0
85
90
85
2i
6
1a
2.5
6.5
2.5
7.0
2.5
7.0
2.0
6.5
85
82
85
80
90
75
86
78
2i
2i
6
Br
O
O
O
O
O
O
Br
2
3
4
1b
2a
2b
3a
3b
4a
4b
Br
O
O
Br
8
Br
Br
Cl
Cl
Br
O
O
O
O
4.0
4.5
85
80
2g
Br
6
Br
O
O
Br
O
O
O
5
6
Br
O
O
6
CO2Et
O
CO2Et
Br Br
O
Br
O
Br
4.0
95
7
2g
7
Br Br
O
O
O
O
COOEt
COOEt
O
7
2.0
2.0
2.5
2.0
2.0
2.0
2.0
1.5
70
85
85
90
95
90
85
70
9
7
Br
Br
Br
Br
O
O
O
O
O
8
EtO
Br
Br
7
EtO
Br
O
O
O
O
O
O
O
9
EtO
OEt
EtO
OEt
Br
Br
Br
5a
5b
2.5
7.0
75
70
Br
O
O
O
O
O
O
O
O
O
10
11
12
13
14
7
Ph
Ph
Ph
Ph
Br
O
O
Br
O
O
O
O
Br
O
2i
11
7
Ph
O
Ph
O
O
Br
O
O
O
O
6a
6b
7a
2.0
5.0
85
85
2i
2i
EtO
EtO
Br Br
Br
I
O
O
O
O
O
I
O
EtO
EtO
Ph
Br Br
O
O
O
O
O
O
COOEt
COOEt
9
2.0
5.5
85
80
7
7
Ph
Ph
Ph
Ph
Ph
I
Br
Br Br
O
O
O
O
O
O
O
O
7b
15
2.0
90
9
Ph
Ph
Ph
Ph
Ph
Ph
Br Br
I
a
a
The yields refer to those of pure isolated products characterized by IR,
1H and 13C NMR spectroscopic data.
The yields refer to those of pure isolated products characterized by IR,
1H and 13C NMR spectroscopic data.

B. C. Ranu et al. / Tetrahedron 63 (2007) 155–159
157
Table 3. Stereoselective debromination–eliminationn of vic-bromo acetates catalyzed by [pmIm]BF4
Entry
Substrate
Time (min)
Product
Ph
Yield (%)a
82
Ref.
5b
Br
Ph
1
3
Ph
OAc
Ph
(meso)
(dl)
Br
Ph
Ph
Ph
2
3
4
5
6
7
8
3.5
67
80
85
80
60
82
85
5b
4j
OAc
Ph
OAc
O
O
Ph
O
Ph
3
Br
O
O
(erythro)
O
O
OAc
O
Ph
3
4j
Ph
Br
MeO
MeO
(erythro)
OAc
O
O
Ph
3
4j
Ph
Br
O
(erythro)
OAc
O
3
4j
Ph
S
Ph
Br
S
(erythro)
OAc
O
O
OEt
OEt
3
10
10
Br
O
O
(erythro)
O
O
OAc
O
O
OEt
OEt
OEt
3
Br
MeO
MeO
BnO
(erythro)
OMe
OMe
OAc
O
O
O
OEt
9
3.5
85
80
10
10
Br
BnO
(erythro)
OMe
OMe
OAc
O
OEt
OEt
10
3
Br
MeO
MeO
(threo)
The yields refer to those of pure isolated products characterized by IR, 1H and 13C spectroscopic data.
a
monobromo products contain 2–5% of the corresponding
doubly debrominated ketones; however, pure compounds
were obtained easily by chromatographic purification. On the
other hand, debrominated compounds were obtained in high
purity after just a simplework up. a-Monobromoketones also
underwent facile debromination to the parent ketone when
exposed to this procedure. The results are reported in Table 2.
It was observed that chloride remained inert under the reac-
tion condition (entry 3, Table 2) while iodides were rapidly
removed (entries 12–14, Table 2). Thus, this procedure can
lead to the selective removal of a bromide in the presence of
a chloride functionality. By simple manipulation this reaction
was also successfully utilized for stereoselective olefin for-
mation by debromination–elimination of vic-acetoxybromo

158
B. C. Ranu et al. / Tetrahedron 63 (2007) 155–159
Table 4. Results of debromination with conventional reagents
protocol for highly selective debromination of gem-a-di-
bromoketones to monobromoketones or debromoketones
by proper control of reaction time. To the best of our knowl-
edge, we are not aware of any such use of ionic liquid for this
transformation. The significant advantages offered by this
procedure are operational simplicity, fast reaction, high
selectivity, excellent yields of products, no reduction of other
reducible functionalities, recyclable catalyst and use of no
organic solvent and toxic reagent in the reaction. We believe,
this reaction will find suitable applications in organic syn-
thesis and will lead to further useful chemistry.
O
O
O
O
+
+
Br
Br
Br
Br
Br
A
C
B
Reducing agent
Time (h), condition Ratio of A, B and C
(nBu)3SnH2j
12, reflux (85 ꢀC)
12, rt
9, rt
42:58:00
24:61:15
40:32:28
10:65:21
NaI, TMSCl2e
Zn in AcOH(1 equiv)2k
Ph3P (1.2 equiv) in
CH3OH and C6H6
12, reflux
2a
derivatives.5 The results are summarized in Table 3. Interest-
ingly, only (E)-alkenes were obtained from all the substrates
illustrated in Table 3 in accordance with the earlier observa-
tions in the debromination of vic-dibromides by this ionic
liquid, [pmIm]BF4.4j
4. Experimental
4.1. General
The ionic liquid, [pmIm]BF4, was prepared by the metathe-
sis reaction of [pmIm]Br12a with NaBF4 following a reported
procedure.12b The dibromides were prepared following
known procedures.13a,b IR spectra were taken as thin films
for liquid compounds and as KBr pellets for solids. H and
13C NMR spectra were recorded in CDCl3 solutions at 300
and 75 MHz, respectively.
The selective debromination of gem-dibromoketones to
monobromoketones by this reagent is unique since no reports
of such selectivity for this transformation have been found in
the literature. Our own findings on the use of conventional
reagents for this debromination reaction were also very dis-
appointing (Table 4). None of these reagents showed appre-
ciable selectivity towards monodebromination.
1
4.1.1. General experimental procedure for the debromi-
nation of gem-a-dibromoketones; representative one
for debromination of 2,2-dibromo-1-phenylethanone
(entry 1, Table 1). A mixture of 2,2-dibromo-1-phenyletha-
none (277 mg, 1 mmol) and ionic liquid, 1-methyl-3-pentyl-
imidazolium tetrafluoroborate, [pmIm]BF4 (1.2 g, 5 mmol)
mixed with one drop of H2O was subjected to microwave ir-
radiation in a microwave reactor (CEM Corporation, 300 W,
125 ꢀC, 50 psi) for 2.5 min (TLC). The reaction mixture was
allowed to cool and extracted with ethyl acetate (3ꢁ5 mL).
Evaporation of the solvent left the crude product, which was
purified by column chromatography (hexane–ethyl acetate,
97:3; Rf for monobromo compound: 0.32 and Rf for doubly
debrominated compound: 0.27) to give the pure mono-
bromo-product, 2-bromo-1-phenylethanone (169 mg, 85%)
The ionic liquid, [pmIm]BF4, plays a vital role in this trans-
formation as no reaction was observed in the absence of
ionic liquid. It was also found that this reaction did not pro-
ceed at all at room temperature or under conventional heat-
ing. A similar imidazolium based ionic liquid, [pmIm]Br,
also catalyzed this reaction; however, the reaction with
[pmIm]BF4 was both faster and cleaner. Thus, this ionic liq-
uid was chosen for all the reactions. As mentioned earlier,
the ionic liquid remained intact after the reaction and was re-
cycled in subsequent runs without any difficulty. In consid-
eration of all these views, probably the reaction is going
through an enolate formed by abstraction of one bromonium
ion, which was then protonated by traces of H2O present in
the ionic liquid. This hypothesis gets support by the isolation
of the deuterated bromoketone and ketone from a reaction
carried out in the presence of D2O (Scheme 2).
as a colorless oil. IR (neat) 3057, 1697 cmꢂ1; H NMR
1
d 4.43 (s, 3H), 7.41–7.46 (m, 2H), 7.53–7.58 (m, 1H),
7.91–7.94 (m, 2H); 13C NMR d 190.9, 133.8, 133.7, 128.7
(2C), 128.6 (2C), 31.1. These values are in good agreement
with the reported data.2i
O
O
O
[pmIm] BF4
D2O, 4 min
+
When this reaction was irradiated for 6.5 min, the com-
pletely debrominated product, acetophenone (Rf value:
0.27) (82%) was obtained. The spectroscopic data were in
good accord with those of an authentic sample.
Br
Br
D
Br
D
D
Scheme 2.
In general, reactions by this procedure are very clean, high
yielding and fast. Although, the reaction proceeds with a
5 mol %ofionicliquid, thebestconditionforacleanandfaster
reaction was found by using 5 equiv of ionic liquid. One good
feature ofthis reagent is thatreduciblegroupssuch as carbonyl
and carboxylic ester are safe under this procedure, as this ionic
liquid does not function like a conventional reducing agent.
This procedure was followed for all the reactions listed in
Tables 1–3. All these products except compounds in entries
(Table 1) and entry (Table 2) are known compounds and their
1
spectroscopic data (IR, H and 13C NMR) were identical
with those reported (references in Tables 1–3).2i,g,6–11,5b,4j,
The spectroscopic data of these three compounds and ele-
mental analysis were provided below:
3. Conclusion
4.1.2. 1-Benzo[1,3]dioxol-5-yl-2-bromoethane (entry 5a,
Table 1). White solid, mp (pet ether) 90–93 ꢀC; IR (KBr)
2999, 2952, 2914, 1683, 1602, 1504, 1488, 1288, 1248,
This procedure using an easily accessible ionic liquid,
[pmIm]BF4, as catalyst demonstrates a novel and efficient
933, 765 cmꢂ1 1H NMR (300 MHz, CDCl3) d 4.39 (s,
;

B. C. Ranu et al. / Tetrahedron 63 (2007) 155–159
159
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2H), 6.08 (s, 2H), 6.09 (d, 1H, J¼8.2 Hz), 7.46 (s, 1H), 7.60
(d, 1H, J¼8.2 Hz); 13C NMR (75 MHz, CDCl3) d 31.0,
102.5, 108.5, 108.9, 126.0, 129.0, 148.8, 152.9, 189.9.
Anal. Calcd for C9H7BrO3: C, 44.47; H, 2.9. Found: C,
44.09; H, 2.6.
4.1.3. 1-Benzo[1,3]dioxol-5-yl-ethanone (entry 5b, Table1).
White solid, mp (pet ether) 84–86 ꢀC; IR (KBr) 3072, 2974,
2916, 2854, 1662, 1602, 1448, 1348, 1282, 1114, 855, 709,
603 cmꢂ1; 1H NMR (300 MHz, CDCl3) d 2.42 (s, 3H), 5.91
(s, 2H), 6.75 (d, 1H, J¼8.3 Hz), 7.30 (s, 1H), 7.45 (d, 1H,
J¼8.3 Hz); 13C NMR (75 MHz, CDCl3) d 26.7, 102.2,
108.1, 108.2, 125.1, 132.4, 148.5, 152.1, 196.5. Anal. Calcd
for C9H8O3: C, 65.85; H, 4.91. Found: C, 65.79; H, 4.88.
3. (a) Welton, T. Chem. Rev. 1999, 99, 2071; (b) Wasserscheid,
P.; Keim, W. Angew. Chem., Int. Ed. 2000, 39, 3773; (c)
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Leonard, N. M.; Mohan, R. S. Org. Lett. 2003, 5, 55; (e)
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Gu, D.-G.; Ji, S.-J.; Jiang, Z.-Q.; Zhou, M.-F.; Loh, T.-P.
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4. (a) Ranu, B. C.; Das, A.; Samanta, S. J. Chem. Soc., Perkin
Trans. 1 2002, 1520; (b) Ranu, B. C.; Dey, S. S. Tetrahedron
Lett. 2003, 44, 2865; (c) Ranu, B. C.; Dey, S. S.; Hajra, A.
Tetrahedron 2003, 59, 2417; (d) Ranu, B. C.; Dey, S. S.
Tetrahedron 2004, 60, 4183; (e) Ranu, B. C.; Das, A. Aust. J.
Chem. 2004, 57, 605; (f) Ranu, B. C.; Jana, R.; Dey, S. S.
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4.1.4. (4-Acetyl-phenoxy)acetic acid ethyl ester (entry 5,
Table 2). Colorless oil; IR (neat) 2983, 2937, 1755, 1678,
1600, 1508, 1427, 1359, 1271, 1174, 1116, 985, 837 cmꢂ1
;
1H NMR (300 MHz, CDCl3) d 1.06 (t, 3H, J¼7.1 Hz),
2.30 (s, 3H), 4.03 (q, 2H, J¼7.1 Hz), 4.47 (s, 2H), 6.71 (d,
2H, J¼8.8 Hz), 7.71 (d, 2H, J¼8.8 Hz); 13C NMR
(75 MHz, CDCl3) d 14.4, 26.6, 61.8, 65.4, 114.6, 130.8,
131.4, 161.8, 168.5, 196.9. Anal. Calcd for C12H14O4: C,
64.85; H, 6.35. Found: C, 64.77; H, 6.30.
The ionic liquid remaining in the flask was rinsed with ethyl
acetate and dried under vacuum at 80 ꢀC to be used for sub-
sequent reactions. This can be used for reactions for up to
five runs without any appreciable loss of efficacy. After
five runs, about 50% fresh ionic liquid was added to it, and
the mixture was found to be good for several more reactions.
5. (a) Inoue, A.; Maeda, K.; Shinokubo, H.; Oshima, K.
Tetrahedron 1999, 55, 665; (b) Cho, S.; Kang, S.; Keum, G.;
Kang, S. B.; Han, S.-Y.; Kin, Y. J. Org. Chem. 2003, 68, 180.
6. Rahman, M. T.; Kamata, N.; Matsubara, H.; Ryu, I. Synlett
2005, 2664.
Although, the representative procedure is based on a milli-
gram scale, it has been scaled up to multigram level without
any difficulty.
7. Meshram, H. M.; Reddy, P. N.; Vishnu, P.; Sadashiv, K.; Yadav,
J. S. Tetrahedron Lett. 2006, 47, 991.
8. Kim, J. H.; Kim, H. R.; Ryu, E. Synth. Commun. 1990, 20,
1625.
Acknowledgements
9. Jereb, M.; Zupan, M.; Stavber, S. Chem. Commun. 2004, 2614.
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This investigation has enjoyed financial support from CSIR
[grant no. 01(1936)/04], New Delhi. K.C. and R.J. are also
thankful to CSIR for their fellowships.
12. (a) Namboodiri, V.; Varma, R. S. Org. Lett. 2002, 4, 3161; (b)
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References and notes
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