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Bromination of ketones with H2O2–HBr ‘‘on water’’{

Ajda Podgoršek,a Stojan Stavber,a Marko Zupanab and Jernej Iskra*a
Received 10th May 2007, Accepted 11th July 2007
First published as an Advance Article on the web 7th August 2007
DOI: 10.1039/b707065a

Various 1,3-diketones, b-ketoesters, cyclic ketones, aryl alkyl and dialkyl ketones were effectively
brominated with an aqueous H2O2–HBr system ‘‘on water’’ at room temperature without the
need for a catalyst or organic solvent. The resultant brominated ketones were isolated in yields of
69–97% with high selectivity for monobromination vs. dibromination. Reactivity was
Published on 07 August 2007 on http://pubs.rsc.org | doi:10.1039/B707065A

manipulated by using more diluted aqueous solutions of H2O2 and HBr and the use of an excess
of HBr where necessary. Dilution also increases selectivity of ring bromination vs. a-bromination
of aryl ketones with an activated phenyl ring. Finally, an aqueous H2O2–HBr system was used for
a tandem oxidation–bromination process and alcohols were transformed into a-bromoketones.
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This simple but effective ‘‘on water’’ bromination of ketones with an aqueous H2O2–HBr system
is characterised by the use of inexpensive reagents, a lower impact on the environment and the
absence of organic waste that make it a good alternative to existing bromination methods.

Introduction agents. Also, bromination in the presence of H2O2 allows

a-Bromination of carbonyl compounds is an important
reaction in organic synthesis as the resulting a-bromo-ketones
are used in the synthesis of variety of molecules, including
biologically active compounds.1 A number of various bromi-
nation protocols of carbonyl compounds have been developed,
including the use of molecular bromine or its complexes in the
presence of protic or Lewis acid.2 The use of molecular
bromine has several drawbacks arising out of its hazardous
nature, difficult handling, low atom efficiency, low selectivity
and the formation of HBr as a by-product. Alternative
brominating agents, such as tetralkylammonium tribromides3
and N-bromosuccinimide,4 have been increasingly used for
a-bromination of carbonyl compounds resulting in easier
handling and increased selectivity of the reaction. Never-
theless, these brominating reagents have some limitations
including their low atom efficiency, the need for reagent
residue removal and that molecular bromine is required for
their preparation.
To fulfil increasing demands for ‘‘green’’ chemistry and to
achieve higher efficiency and selectivity of the reactions,
researchers are focusing on the development of sustainable
and ecologically more acceptable bromination protocols based
on the oxidation of the bromide salt with a suitable oxidant.5,6
Rothenberg and Clark have made an important study on the
best choice of bromine atom (Br2 vs. HBr vs. MBr–acid) in
oxybromination reactions, including large-scale bromina-
tion.5b Amongst oxidants, hydrogen peroxide is a valuable
oxidant since water is the only effluent of the process
(Scheme 1). Moreover, the molar mass and cost of H2O2 are
much lower than those of bromine and other brominating
a
‘‘Jožef Stefan’’ Institute, Jamova 39, 1000, Ljubljana, Slovenia.
E-mail: jernej.iskra@ijs.si; Fax: +386 1 4773 811; Tel: +386 1 4773 631
b
Faculty of Chemistry and Chemical Technology, University of
Ljubljana, Aškerčeva 5, 1000, Ljubljana, Slovenia
{ Electronic supplementary information (ESI) available: Experimental
details. See DOI: 10.1039/b707065a
complete utilization of bromine atoms and therefore the atom
economy is much higher. While oxidative bromination with
hydrogen peroxide has been known since 1924,7 it still attracts
considerable attention for electrophilic bromination8,9,10
as well as for free-radical processes.11 However, there are
only separate examples of oxidative bromination of
ketones.8c,10c,10d Recently, b-dicarbonyl compounds were
oxybrominated with NH4Br catalyzed by V2O512 and with
KBr and concentrated HCl in toluene.13 In contrast,
acetophenones could only be converted to a,a-dibromoaceto-
phenones with HBr–H2O2 in boiling dioxane.14
While the aforementioned methods use organic solvents,
such as dichloromethane, dioxane and toluene, which have
serious environmental impacts, and involves a laborious work-
up procedure, we report how an aqueous H2O2–HBr system
without added catalyst is an efficient and ‘‘greener’’ method
for a-bromination of 1,3-diketones, b-ketoesters and ketones
under mild, organic solvent-free and organic waste-free condi-
tions (Scheme 1). The utilization of this brominating system in
aqueous phase resembles the action of haloperoxidases, where
bromination takes place at an active site providing that local
concentration of reactants is sufficiently high.
Scheme 1
Results
Oxidative bromination is based on the in situ oxidation of HBr
into bromine (eqn (1)), which then acts as the brominating
agent (eqn (2)). However, bromine also catalyzes the decom-
position of H2O2 (eqn (3)), and consequently a higher amount
of H2O2 is needed to compensate for this. In our study, to

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minimize this decomposition, we evaluated various modes of

reagent addition for the bromination of two model substrates:
acetophenone 1a and b-ketoester 2a.

H2O2 + 2HBr A Br2 + 2H2O (1)

S–H + Br2 A S–Br + HBr (2)

Br2
2 H2 O2 DCCA 2 H2 OzO2 (3)
or HBr

Reactions were performed at room temperature by adding

an appropriate amount of 30% aqueous solution of H2O2 and
48% aqueous solution of HBr to a stirred suspension of 1 mmol
Published on 07 August 2007 on http://pubs.rsc.org | doi:10.1039/B707065A

of ketone 1a or 2a in 0.5 mL of water (Table 1). Results show

that the stepwise addition of H2O2 (Method B) produced
Fig. 1 Time dependence of concentration of bromine and hydrogen
higher yields of brominated products 1b and 2b than when peroxide in 8% H2O2 and 9% HBr aqueous solution.
H2O2 was added in a single addition (Method A). This effect is
more pronounced in the case of the less reactive ketone 1a.
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reaction mixture during the reaction would allow good

Improved reaction conditions comprise the stepwise addition
conversion of the ketone using a smaller amount of H2O2.
of HBr and H2O2 (Method C, Table 1). Therefore, reaction of
First, we brominated the ketones with either activated
ketones 1a and 2a with 2 equiv. of H2O2 and 1.5 equiv. of HBr
methylene or the methyne group with an aqueous H2O2–HBr
using Method C gave a-brominated products 1b and 2b in 85%
system. The reaction of various 1,3-diketones was achieved by
and 95% isolated yields, respectively, while the further excess
stepwise addition of 1 equiv. of 48% aqueous HBr and 2 equiv.
of H2O2 up to 2.5 equiv. did not significantly influence the
of 30% aqueous H2O2 (Method C, the initial addition of
conversion; even with an excess of HBr no formation of the
reagents yielded an aqueous reaction mixture of 3% H2O2 and
dibromo ketone was observed.
6% HBr) into a stirred mixture of 1 mmol of ketone in 0.5 mL
We confirmed the importance of the gradual addition of
of water at room temperature (Table 2). Under these
H2O2 by following its decomposition upon mixing with HBr
conditions bromination of 2-methylcyclohexane-1,3-dione 3a,
(Fig. 1). For the system, where the initial concentration of
5,5-dimethylcyclohexane-1,3-dione 4a and 1,3-diphenylpro-
H2O2 and HBr were 8% and 9%, respectively (conditions used
pane-1,3-dione 5a took place selectively and only monobro-
for bromination of ketones in our experiments) it was shown minated products were isolated in good yields. Only the
that 50% of the maximum quantity of bromine is formed reaction with 1-phenylbutane-1,3-dione 6a produced a small
within minutes. However, H2O2 constantly decomposes so that amount of the dibrominated product 6c. b-Ketoester 7a was
after three hours only 23% of the initial quantity of H2O2 brominated under identical reaction conditions, while for 8a a
remained. Therefore, the stepwise addition of H2O2 into the longer reaction time and 2 equivalents of HBr were necessary.
We found the method using an aqueous H2O2–HBr system
Table 1 The effect of the mode of addition of H2O2 and HBr on as a brominating agent to be applicable also to the cyclic
bromination of ketones 1a and 2a
ketone 9a. The reaction was performed with a 10% excess of
HBr without the addition of 0.5 mL of water (addition of first
portion of reagents yielded an aqueous reaction mixture of
12% H2O2 and 29% HBr) and the corresponding brominated
product 9b was formed in good yield after 24 h. We also tested
the method on several less reactive substrates including aryl
alkyl and dialkyl ketones to determine its limitations.
Product H2O2 : HBr Methoda Conv.b (%) 4-Methylacetophenone 10a showed good reactivity, with 10%
excess of HBr resulting in an 80% conversion. Higher amounts
1bc 2:1 A 60
2:1 B 70 of HBr (1.5 equiv.) lowered the selectivity of the reaction, and
2:1 C 80 also the a,a-dibrominated product 10c was formed in small
2.5 : 1 C 80 amounts. The acetophenones 11a and 12a were effectively
2 : 1.5 C 89 (85) brominated using 1.5 equiv. of HBr and water as a solvent.
2.5 : 1.5 C 87
2bd 2:1 A 85 Functionalization of the less reactive derivatives 13a and 14a
2:1 B 88 was effective when the amount of HBr was increased to 2
2:1 C 93 equivalents and without additional water.
2.5 : 1 C 95
2 : 1.5 C 100 (95) Finally, we found that dialkylketones 15a–17a could also
a
Method A: H2O2 and HBr were added in one portion. Method B:
be effectively brominated. Unsymmetrical acyclic ketone
H2O2 was added gradually (0.5 equiv. per 3 h). Method C: H2O2 heptyl(methyl)ketone 16a preferentially reacted at a more
and HBr were added gradually (0.5 equiv. per 3 h). b Determined by substituted carbon atom yielding 3-bromononan-2-one 16b
1
H NMR spectroscopy; yields in parentheses refer to isolated yields. and 1-bromononan-2-one 16d in a yield of 49% and 21%,
c
Reaction time 24 h. d Reaction time 9 h.
respectively.

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Table 2 a-Bromination of various ketones in aqueous H2O2–HBr We further upgraded our ‘‘green’’ approach to bromination
system by adopting an environmentally friendly work-up procedure.
The absence of organic waste and an organic solvent in the
reaction enabled simple isolation comprised of filtration for
solid products, or the addition of a minimum quantity of non-
chlorinated organic solvent, drying agent and filtration of
insoluble material for liquid products. On a larger scale
Product H2O2 : HBr Time Yield (%)a
experiment, the work-up procedure was simple and required
only the separation of the denser bromo ketone layer from the
aqueous phase without the need for an organic solvent (see
Table 4, 23a).
Next, we investigated the effect of water on the regioselec-
tivity of the bromofunctionalization of phenylalkanones 18a–
Published on 07 August 2007 on http://pubs.rsc.org | doi:10.1039/B707065A

3b R1LCH3, R2LR3LH 2:1 8h 95 (90) 20a (Table 3) and benzocycloalkanones 21a–24a (Table 4) with
4b R1LH, R2LR3LCH3 2:1 8h 90 (87) H2O2–HBr. Bromination of 18a occurred at the side chain
regardless of the addition of water (Table 3). Introduction of a
methoxy group on the para position of the phenyl ring altered
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the regioselectivity of the reaction; 19a preferentially reacted

5b R1LPh 2:1 9h 85 (82) on the aromatic ring (19b : 19d = 1 : 4.6) while an higher
6b R1LCH3 2:1 9h 81 (79)b amount of water in the reaction mixture promoted only ring
bromination and 19d was obtained, when isolated, in yield of
95% . Functionalization of 4-aryl-2-butanone 20a, with the less
activated a-position, was selectively performed on the aro-
7b 2:1 8h 90 (85) matic ring even without added water.

Table 3 The effect of water on the regioselectivity of bromination of

phenylalkanones in aqueous H2O2–HBr system

8b 2:2 24 h 100 (95)

9b 2 : 1.1c 24 h 73 (69)

a
Mol. equiv. Added Distribution
Substrate H2O2 : HBr water a:b:d
10b 2 : 1.1 24 h 80 (78)
18a RLH, n = 1 2:2 No 7 : 93(88) : —
2:2 Yes 13 : 87 : —
19a RLOCH3, n = 1 2:1 No — : 18 : 82
2:1 Yes 3 : — : 97(95)
20a RLOCH3, n = 2 2:1 No — : — : 100
11b R1LPh 2 : 1.5 24 h 94 (88)
2:1 Yes — : — : 100(96)
12b R1LCH2Ph 2 : 1.5 24 h 94 (86) a
13b R1LCH3 2 : 2c 24 h 80 (78) Determined by 1H NMR spectroscopy; yields in parentheses refer
14b R1Lcy-Butyl 2 : 2c 24 h 80 (76) to isolated yields after column chromatography.

Similarly, indanone 21a and tetralone 23a were brominated

only on the side chain (Table 4), while their methoxy
15b R1LR2LPropyl 2:2 24 h 82 (80) derivatives 22a and 24a were brominated preferentially on
16b R1LHeptyl,R2LCH3 2:1 24 h 49d the aromatic ring. Again, the addition of water completely
retarded a-bromination and only the ring-brominated pro-
ducts 22d and 24d were formed. NBS showed a similar
activation of aromatic bromination in water vs. neat.4c
17b 2:2 24 h 81 (77) Activation of ring bromination is even stronger in the system
a
Method C; yields are based on starting compound; yields in HBr–H2O2 since dibromination is observed.
parentheses refer to isolated yields. b 9% (5%) of 2,2-dibromo-1- This bromination protocol could enable tandem oxidation–
phenyl-butane-1,3-dione 6c was formed. c Without addition of water. bromination of alcohols to synthesize a-bromo ketones
d
21% of 1-bromononan-2-one 16d was formed.
directly from sec-alcohols. HBr alone catalyzes oxidation of

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alcohols with 30% aq. H2O2 but it is difficult to selectively
oxidize the alcohol into the ketone without its concomitant
bromination (Table 5, entries 1–4), although it is claimed
otherwise.15 Alternatively, using higher amount of reagents
(H2O2 and HBr were used in ratio 4 : 1.7) resulted in yields of
a-bromoacetophenone 1b of 83% and 93% in 24 and 48 h,
respectively (Table 5, entries 5 and 6). Tandem oxidation–
bromination worked well for the other tested sec-alcohols, 26
and 27 (Table 5, entries 7–9).
Table 4 The effect of water on the regioselectivity of bromination of
benzocycloalkanones in aqueous H2O2–HBr system
Published on 07 August 2007 on http://pubs.rsc.org | doi:10.1039/B707065A
evaluate the influence of water on the bromination of
b-dicarbonyl compounds and ketones in an aqueous H2O2–
HBr system. While this process proceeds through an
enol, we predicted that water activates the reaction by
promoting the formation of the enol form. This was
confirmed by 1H NMR studies in the case of the reactive
substrate, such as b-ketoester 8a. A 1H NMR experiment in
CDCl3 solution indicated that only 5% of 8a is present in
the enol form (Fig. 2, spectrum A). However, in an
aqueous solution (D2O : DMSO, 3 : 2) the entire amount of
the enol form increased to 44% (Fig. 2, spectrum B), while the
addition of 0.5 equiv. of HBr did not have a significant
influence (Fig. 2, spectrum C). In the case of the less reactive

ketone 1a, the concentration of the enol form is too low to be

observed by 1H NMR. To evaluate the influence of water on
this reaction, bromination of acetophenone 1a was performed
in CHCl3 and the results compared to the reaction in the
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aqueous phase. Oxidative bromination of 1a in chloroform

Mol. equiv. Added Distributiona proceeded with only 10% conversion, compared to 89% in
Substrate H2O2 : HBr water a:b:d
water (Scheme 2). Both the aforementioned findings indicate
21a RLH, n = 1 2 : 1.1 No 3 : 90(87)b : — that water plays an important role in the activation of the
2 : 1.1 Yes 6 : 88b : — a-bromination process.
22a RLOCH3, n = 1 2 : 1 No 27 : 17 : 49c
2 : 1 Yes 24 : — : 61c
23a RLH, n = 2 2 : 1.1 No 7 : 93(90) : —
2 : 1.1d Yes 5 : 95(88) : —
24a RLOCH3, n = 2 2 : 1 No 13 : 28 : 49e
2 : 1 Yes 20 : — : 64e
a
Determined by 1H NMR spectroscopy; yields in parentheses refer
to isolated yields. b 7% (4%) and 6% of a,a-dibromoindanone 21c
was formed, respectively. c 7% and 15% of 4,6-dibromo-5-methoxy-
indanone was formed (dH 7.94 ppm (s, 1H, ArH)), respectively.
d
Large scale experiment and organic solvent-free isolation. e 10%
and 16% of 5,7-dibromo-6-methoxy-tetralone (dH 8.22 ppm (s, 1H,
ArH)) was formed, respectively.

Table 5 Oxidation and a-bromination in aqueous H2O2–HBr system

H2O2 : Distributiona
Entry sec-Alcohol HBr Time sec-alcohol : a : b

1 1-phenyl-ethanol 25 2 : 0.1b 0.75 h 17 : 73 : 10

2 2 : 0.1 30 h 46 : 54 : —
3 2 : 0.2 16 h 13 : 85 : 2
4 2 : 0.2 24 h — : 87 : 13
5 4 : 1.7 24 h — : 17 : 83
6 4 : 1.7 48 h — : 7 : 93 (90)
7 cycloheptanol 26 4 : 1.5 10 h — : 7 : 93 (88)
8 3-pentanol 27 4 : 1.5 10 h — : — : 97 (92)
a
Distribution determined by 1H NMR spectroscopy. Isolated yield
in parenthesis. b 80 uC.

Discussion
Recent reports have shown that some reactions are accelerated Fig. 2 1H NMR spectra of ethyl 2-benzyl-3-oxobutanoate 8a in
in the presence of water in comparison to those in organic CDCl3 (spectrum A), D2O : DMSO 3 : 2 (spectrum B) and in D2O :
solvent or without solvent.16,17 In this study, we wanted to DMSO 3 : 2 with addition of 0.5 equiv. of HBr (spectrum C).

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Scheme 2
Conclusion
1,3-Diketones, b-ketoesters and ketones were successfully
brominated at room temperature in an aqueous H2O2–HBr
system without a catalyst with high selectivity for mono-
Published on 07 August 2007 on http://pubs.rsc.org | doi:10.1039/B707065A
bromination vs. dibromination. Reactivity could be manipu-
lated by addition of water, i.e. using a more diluted aqueous
solution of HBr and H2O2. This approach also increases
selectivity of ring bromination vs. a-bromination, when the
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phenyl ring is activated with an electron donating group like a
methoxy group. The ‘‘green’’ features of this protocol include
the use of inexpensive reagents and a lower impact on the
environment, since bromine is generated in situ from H2O2 and
HBr. The use of H2O2 as a ‘‘green’’ oxidant produces water as
the only by-product of the reaction. All these advantageous
features make the procedure organic waste-free and organic
solvent-free and therefore a good alternative to existing
bromination methods. The results presented here also demon-
strate that water is not just a good reaction media for
a-bromination of carbonyl compounds but also plays an
important role in the activation of the ketone group for
a-bromination. Furthermore, the H2O2–HBr system could be
used for tandem oxidation–bromination and to synthesize
a-bromoketones directly from alcohols.
Experimental
Reaction procedure for bromination of ketones 1a and 2a in
aqueous H2O2–HBr system
Method A. Ketone 1a or 2a (1.0 mmol) was suspended in
water (0.5 mL) and the flask was covered with aluminium foil.
A 48% aqueous solution of HBr (0.114 mL, 1.0 mol equiv.)
and 30% aqueous solution of H2O2 (0.204 mL, 2.0 mol equiv.)
were added in one portion and the mixture was stirred at room
temperature. The progress of the reaction was monitored by
TLC. After 24 h in the case of 1a and 9 h in the case of 2a, the
reaction mixture was dissolved in 5 mL of a mixture of hexane
and ethylacetate (20 : 1 or 10 : 1), then solid NaHSO3 was
added to reduce unreacted Br2 and H2O2 and the solution
was dried over anhydrous Na2SO4. The insoluble material was
filtered off and the organic solvent evaporated under reduced
pressure. The crude reaction mixture was then analyzed by 1H
NMR spectroscopy. Finally, products were isolated by column
chromatography and the structure determined by comparison
with the literature data.
Method B. Ketone 1a or 2a (1.0 mmol) was suspended in
water (0.5 mL) and the flask was covered with aluminium foil.
Then 48% aqueous solution of HBr (0.114 mL, 1.0 mol equiv.)
was added in one portion, while 30% aqueous solution of H2O2
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(0.204 ml, 2.0 mol equiv.) was added gradually (0.051 mL,
0.5 mol equiv.) over a period of 2–3 h. The mixture was then
stirred at room temperature and the progress of the reaction
monitored by TLC. At the end of the reaction the work-up
procedure follows that of Method A.
Method C. Ketone 1a or 2a (1.0 mmol) was suspended in
water (0.5 mL) and the flask was covered with aluminium foil.
A 48% aqueous solution of HBr (0.057 mL, 0.5 mol equiv.)
was added. After stirring the mixture at room temperature
for 5 min, 30% aqueous solution of H2O2 (0.051 mL,
0.5 mol equiv.) was added. This procedure (0.5 mol equiv.
HBr, stirring for 5 min, 0.5 mol equiv. H2O2) was then
repeated every 2–3 h until an appropriate amount of bromide
and oxidant were added. The progress of the reaction was
monitored by TLC. After completion of the reaction the work-
up procedure follows that of Method A.
Typical reaction procedure for bromination of ketones in
aqueous H2O2–HBr system
The substrate (1.0 mmol) was suspended in 0.5 mL of water (in
case of performing reaction with additional water) and the
flask was covered with aluminium foil to shield the reaction
mixture from light. A 48% aqueous solution of HBr (0.057 mL,
0.5 mol equiv.) was added. After stirring the mixture at
room temperature for 5 min, 30% aqueous solution of H2O2
(0.051 mL, 0.5 mol equiv.) was added. This procedure (0.5 mol
equiv. HBr, stirring for 5 min, 0.5 mol equiv H2O2) was then
repeated every 2–3 h until an appropriate amount of bromide
and oxidant were added (Tables 1, 2, 3, and 4). The progress of
the reaction was monitored by TLC. At the end of the reaction
(8 to 24 h), the work-up procedure depended on the aggregate
state of the products.
Work-up procedure for liquid products
The reaction mixture was dissolved in 5 mL of an appropriate
mixture of hexane and ethylacetate (20 : 1 or 10 : 1), solid
NaHSO3 was added to reduce unreacted Br2 and H2O2 and the
solution dried over anhydrous Na2SO4. The insoluble material
was filtered off and then the organic solvent was evaporated
under reduced pressure. The crude reaction mixture was then
analyzed by 1H NMR spectroscopy. Finally, the product was
isolated by column chromatography (SiO2, hexane–EtOAc)
and its structure determined by comparison with the literature
data.
Ethyl 2-bromo-3-oxo-3-phenyl-propanoate (2b, Table 1)4d
2a (192 mg, 1.0 mmol) was transformed using reaction
conditions: 0.204 mL (2.0 mmol) H2O2, 0.171 mL (1.5 mmol)
HBr, 0.5 mL H2O, stirring for 9 h at room temperature.
Column chromatography gave 2b (257 mg, 95%) as a pure
oily product; dH(300 MHz; CDCl3; Me4Si) 1.25 (3H, t, J
7.1 Hz, CH3), 4.29 (2H, q, J 7.1 Hz, CH2), 5.67 (1H, s,
CHBr), 7.47–7.54 (2H, m, ArH), 7.60–7.66 (1H, m, ArH),
7.98–8.01 (2H, m, ArH); dC(76 MHz; CDCl3; Me4Si)
13.6 (CH3), 46.3 (CH2), 63.3 (CHBr), 128.9 (Ar–C), 129.2
(Ar–C), 133.3 (Ar–C), 134.2 (Ar–C), 165.1 (CO), 188.1 (CO);
This journal is ß The Royal Society of Chemistry 2007

m/z (EI, 70 eV) 272 (2%, M++2), 270 (2%, M+), 105 (100%), 77
(57%).
Work-up procedure for solid products
The reaction mixture was filtered off and rinsed with water
(10 mL). The crude reaction mixture was then analyzed by 1H
NMR spectroscopy. Finally, the products were isolated by
column chromatography (SiO2, hexane–EtOAc) or purified by
crystallization and their structures determined by comparison
with the literature data.
2-bromo-5,5-dimethylcyclohexane-1,3-dione (4b, Table 2)2g
Published on 07 August 2007 on http://pubs.rsc.org | doi:10.1039/B707065A
4a (140 mg, 1.0 mmol) was transformed using reaction
conditions: 0.204 mL (2.0 mmol) H2O2, 0.114 mL (1.0 mmol)
HBr, 0.5 mL H2O, stirring for 8 h at room temperature.
Crystallization from EtOH gave 4b (190 mg, 87%) as pure solid
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product; mp 176–177 uC (mp2g 174–176 uC); dH(300 MHz;
CDCl3; Me4Si) 1.12 (6H, s, CH3), 2.48 (4H, s, CH2);
dC(76 MHz; CDCl3; Me4Si) 28.0 (CH3), 32.0 (CH2), 100.6
(CHBr); m/z (EI, 70 eV) 220 (53%, M++2), 218 (53%, M+), 205
(10%), 203 (10%), 164 (100%), 162 (100%), 149 (17%), 147
(17%), 139 (27%), 111 (32%), 83 (73%), 69 (14%), 55 (54%).
Large scale bromination
Water (5 mL) was placed in a conical flask and 48% aqueous
solution of HBr (0.57 mL, 5.0 mmol, 0.5 mol equiv.) was
added, followed by the addition of a-tetralone 23a (1.462 g,
10.0 mmol). The flask was covered with aluminium foil, the
mixture was stirred at room temperature for 5 min before
adding 30% aqueous solution of H2O2 (0.5 mL, 5.0 mmol,
0.5 mol equiv.). This procedure (5.0 mmol of HBr, stirring for
5 min, 5.0 mmol of H2O2) was then repeated every three hours
until an appropriate amount of HBr (11.0 mmol, 1.1 mol
equiv.) and H2O2 (20.0 mmol, 2.0 mol equiv.) were added.
After 24 h, the organic and aqueous phases were separated and
organic phase transferred directly to the column. Column
chromatography (SiO2, n-hexane : EtOAc 20 : 1) gave 23b
(1.981 g, 88%) as pure oily product; 2-bromo-1-tetralone (23b,
Table 4);2g dH(300 MHz; CDCl3; Me4Si) 2.41–2.60 (2H, m,
CH2), 2.90 (1H, dt, J 17.2 and 4.5 Hz, CH2), 3.26–3.37 (1H, m,
CH2), 4.73 (1H, t, J 4.5 Hz, CHBr), 7.25 (1H, d, J 7.9 Hz,
ArH), 7.34 (1H, t, J 7.9 Hz, ArH), 7.51 (1H, td, J 7.9 and J
1.5 Hz, ArH), 8.09 (1H, dd, J 7.9 and 1.4 Hz, ArH);
dC(76 MHz; CDCl3; Me4Si) 26.1 (CH2), 31.9 (CH2), 50.4
(CHBr), 127.1 (Ar–C), 128.6 (Ar–C), 128.7 (Ar–C), 129.9 (Ar–
C), 134.1 (Ar–C), 142.9 (Ar–C), 190.5 (CO); m/z (EI, 70 eV)
226 (18%, M++2), 224 (18%, M+), 144 (33%), 118 (100%), 115
(32%), 90 (42%).
Tandem oxidation and bromination of sec-alcohol
1-Phenyl-ethanol 25 (122 mg, 1.0 mmol) was suspended in
water (0.5 mL) and the flask was covered with aluminium
foil. Then, a 48% aqueous solution of HBr (0.057 mL,
0.5 mol equiv.) was added. After stirring the mixture at room
temperature for 5 min, 30% aqueous solution of H2O2
(0.051 mL, 0.5 mol equiv.) was added. This procedure
(0.5 mol equiv. of HBr, stirring for 5 min, 0.5 mol equiv. of
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H2O2) was then repeated every four hours until an appropriate
amount of HBr (1.7 mol equiv.) and H2O2 (4.0 mol equiv.) had
been added. After 48 h, the crude reaction mixture was isolated
following the work-up procedure for liquid products. Column
chromatography (SiO2, hexane–EtOAc) gave pure solid
product a–bromoacetophenone 1b (178 mg, 90%); mp 48.8–
49.3 uC (mp2g 49–51 uC); dH(300 MHz; CDCl3; Me4Si) 4.46
(2H, s, CH2Br), 7.49 (2H, t, J 7.4 Hz, ArH), 7.61 (1H, tt, J 7.4
and 1.5 Hz, ArH), 7.98 (2H, dd, J 7.4 and 1.5 Hz, ArH);
dC(76 MHz; CDCl3; Me4Si) 30.9 (CH2Br), 128.8 (Ar–C), 128.9
(Ar–C), 133.89 (Ar–C), 133.92 (Ar–C), 191.2 (CO); m/z (EI,
70 eV) 200 (7%, M++2), 198 (7%, M+), 105 (100%), 77 (22%),
69 (12%), 57 (19%).
Acknowledgements
This research was financially supported by the Ministry of
Higher Education, Science and Technology of the Republic of
Slovenia and the Young Researcher program (A.P.) of the
Republic of Slovenia. We are grateful to the National NMR
Centre at the National Institute of Chemistry in Ljubljana and
to the Mass Spectroscopy Centre at the ‘‘Jožef Stefan’’
Institute of Ljubljana.
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