Ultrasonics Sonochemistry 9 (2002) 107±111

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Sonochemical bromination of acetophenones using

p-toluenesulfonic acid±N-bromosuccinimide
M.V. Adhikari, S.D. Samant *
Organic Chemistry Research Laboratory, Division of Applied Chemistry, Department of Chemical Technology, University of Mumbai, Matunga,
Mumbai-400 019, India
Received 15 March 2001; received in revised form 7 May 2001; accepted 23 May 2001

Abstract
Substituted acetophenones react with N-bromosuccinimide (NBS) and p-toluenesulfonic acid (p-TsOH) in the presence of ul-
trasound in methanol at 35  2°C to give a-bromoacetophenones in high yield. In the absence of ultrasound the reaction takes place
at the boiling point of methanol (65°C) and takes longer time. The reaction does not take place in the absence of p-TsOH thermally
or sonically. However the reaction is possible under photochemical conditions in the absence of p-TsOH. The best solvent for the
reaction was found to be methanol. Ó 2002 Elsevier Science B.V. All rights reserved.

Keywords: Acetophenone; Bromination; N-bromosuccinimide; Ultrasound; Sonochemistry

1. Introduction tion of acetophenones with NBS in the presence of ul-

trasound under di€erent conditions.
The bromination of an acyl arene may lead to side
chain a-bromination as well as ring bromination de-
pending upon the conditions employed. The side chain 2. Experimental
bromination has attracted attention due to the potential
of the resulting bromoacetophenones, which are inter- 2.1. Chemicals
mediates for a variety of biologically active compound
[1]. N-bromosuccinimide (NBS) can be employed for the All the chemicals used were of analytical grade. The
a-bromination of ketones [2±4]. The reactions of NBS p-TsOH in the monohydrate form was used as a cata-
are mainly radical reactions, which are further catalyzed lyst. The commercial sample of NBS was puri®ed before
by typical initiators such as light, benzoyl peroxide, 2,20 - use by following the literature procedure [7].
azobisisobutyronitrile (AIBN). NBS is also known to
generate potential bromonium ion in the presence of 2.2. Sonication
a Bronsted acid and the reactions proceed by ionic
mechanism. For example ring bromination of aromatic For the sonication, a rectangular ultrasonic cleaner
compounds has been achieved using NBS±p-toluene- bath was used. It has following speci®cations. Rectan-
sulfonic acid (TsOH) [5]. Recently, it has been reported gular bath: Julabo USR-3 ultrasonic cleaner (Julabo
that ultrasound facilitates ring bromination using NBS Laborotechnik, Germany) (frequency 35 kHz, acoustic
in an acetic acid [6]. This reaction is interesting, as it is a power 85 W, capacity 2.75 L, length 24 cm, breadth 14
typical aromatic electrophilic substitution reaction pro- cm and height 9.5 cm, water level in the bath 6 cm from
ceeding through ionic mechanism. Thus it appears that the bottom). It was well characterized with respect to
ultrasound may facilitate ring as well as side chain pressure intensity pro®les developed when ®lled with
bromination using NBS. Hence we investigated a reac- appropriate amount of water, using the piezoelectric
pressure intensity measurement probe (PPIMP) deve-
*
Corresponding author. Tel.: +91-22-414-5616; fax: +91-22-414- loped in our laboratory [8].
5614. It is known that the maximum cavitation in water
E-mail address: ssd@udct.ernet.in (S.D. Samant). takes place at 35°C [9]. Hence the temperature of the
1350-4177/02/$ - see front matter Ó 2002 Elsevier Science B.V. All rights reserved.
PII: S 1 3 5 0 - 4 1 7 7 ( 0 1 ) 0 0 1 0 8 - 0
108 M.V. Adhikari, S.D. Samant / Ultrasonics Sonochemistry 9 (2002) 107±111

bath was maintained at 35  2°C by adding crushed ice 3. Results

to the bath from time to time and the water level inside
the bath was kept constant. In the present study, acetophenone was used as a
It is known that a ¯at bottom vessel is useful for substrate and all the reaction parameters were optimized
sonochemical reaction. A ¯at bottom Erlenmeyer ¯ask with respect to it.
of 50-ml capacity was used for the reactions.
3.1. Role of p-TsOH
2.3. Speci®cations of the instruments
In order to see the role of p-TsOH, we carried out a
few sets of reactions, the results of which are tabulated
IR spectra were recorded on a JASCO FT-IR spec-
in Table 1. We observed that in the presence of ultra-
trophotometer. The 1 H NMR spectra were recorded on
sound and p-TsOH, conversion was 100% in 2 h and
a Varian XL-300 standard spectrometer. All the melting
71% of a-bromoacetophenone and 29% of m-bromo-
points were taken in an open capillary and using a
acetophenone were getting formed.
Campbell precision melting point apparatus.
3.2. Quantity of p-TsOH
2.4. General procedure for sonochemical bromination of
acetophenones The reaction was carried out using di€erent quantities
of p-TsOH (Table 2). It was observed that for ace-
A model reaction was run as follows. To acetophe- tophenone (10 mmol), NBS (10 mmol) in methanol (20
none (10 mmol) and NBS (10 mmol) taken in the ¯at ml), the amount of p-TsOH required for 100% conver-
bottom ¯ask (50 ml), p-TsOH (1 mmol) in methanol (20 sion was 1 mmol.
ml) was added at once under sonication and stirring.
The reaction was monitored on TLC. At the end of 2 h, 3.3. Solvent
100% conversion was observed.
As monobromoacetophenones ®nd extensive appli- The reaction was carried out using optimized quantity
cations as intermediates in variety of biologically active of p-TsOH and in di€erent solvents like dimethylfor-
compounds, the ratio of NBS to substrate was kept as 1. mamide, dimethylsulfoxide, water, carbon tetrachloride.
Methanol was removed under reduced pressure at These solvents are generally employed for NBS bro-
room temperature. The residue was extracted with di- mination [10]. However, we did not observe any con-
ethyl ether (3  20 ml). The diethyl ether was removed version in any of these solvents.
under reduced pressure at room temperature. The prod-
ucts were separated by preparative TLC. 3.4. Quantity of methanol
In the case of the classical reaction without ultra-
sound the bromination was carried out under identical For acetophenone (10 mmol), NBS (10 mmol), p-
conditions except the application of ultrasound. The TsOH (1 mmol), the quantity of methanol required for
temperature of the reaction mixture was kept at the re- 100% conversion was 20 ml (Table 3).
¯ux temperature of methanol (65°C).
In case of photochemical bromination of acetophe- 3.5. Substrate study
none, the reaction mixture was irradiated with 40-W
tungsten ®lament lamp keeping the other conditions Under optimized conditions a series of substituted
identical. acetophenones was reacted with NBS under sonication

Table 1
Results of reaction of acetophenone with NBS under di€erent conditionsa
Conditions Conversion of 1a(%) Time (h) Combined yield (%) Selectivity (%)
3a ‡ 4a† 3a 4a
, p-TsOH, 30±35°C 61 24 99 99 1
, p-TsOH, 65°C 100 2 98 100 ±
, hm, 30±35°C 100 5 98 100 ±
, hm, 65°C 100 0.5 97 100 ±
, , 30±35°C 0 2 ± ± ±
, , hm, 30±35°C 100 2 96 100 ±
, , p-TsOH, 30±35°C 100 2 99 29 71
p-TsOH ˆ 1 mmol; hm ˆ 40 W tungsten ®lament lamp.
a
Acetophenone (10 mmol), NBS (10 mmol), methanol (20 ml).
 M.V. Adhikari, S.D. Samant / Ultrasonics Sonochemistry 9 (2002) 107±111 109

Table 2 (Table 4). Each reaction was run till 100% conversion
Optimization of the quantity of p-TsOH in the sonochemical bro- was achieved and the products were analyzed. In the
mination of acetophenonea
case of acetophenone 71% a-bromination and 29% m-
p-TsOH Conversion Combined yield Selectivity (%) bromination took place. In all other places only a-bro-
(mmol) of 1a (%) (%) 3a ‡ 4a† 3a 4a mination took place.
1 100 99 29 71
0.9 90 87 23 77
0.8 75 71 16 84
0.6 60 56 18 82
0.5 50 45 16 84 4. Discussion
a
Acetophenone (10 mmol), NBS (10 mmol), methanol (20 ml), so-
nication time (2 h). Acetophenone can undergo electrophilic ring bro-
mination at the m-position as well as electrophilic
a-bromination in the side chain. Electrophilic ring bro-
mination using NBS in the presence of p-TsOH has been
Table 3 achieved [5]. In NBS, N±Br bond is weak. In the pres-
Optimization of the quantity of methanol in sonochemical bromina- ence of acid catalyst like p-TsOH, NBS may undergo
tion of acetophenonea
protonation at the carbonyl oxygen resulting in the
Quantity of Conversion Combined Selectivity (%)
generation of the bromocation as indicated in Scheme 1.
methanol of 1a (%) yield (%) 3a 4a
(ml) 3a ‡ 4a† The bromocation may directly attack at aromatic ring
or a potential nucleophilic center like a-carbon atom of
10 52 44 18 82
15 74 70 13 87 a ketone. Alternatively the bromocation may react with
20 100 99 29 71 a nucleophilic solvent like methanol to form an electro-
a
Acetophenone (10 mmol), NBS (10 mmol), p-TsOH (1 mmol), philic species like CH3 OBr which can react with the enol
sonication time (2 h). form of the ketone to form a-bromo derivative as shown

Table 4
Comparison of NBS bromination of substituted acetophenones under sonochemical and thermal conditionsa
Reactant 1 Productb Ultrasoundc Thermald m.p. (°C) Obs.
Time (h) e
Yield (%) Time (h) Conversion of 1 (%) e
Yield (%) (Rep) [11]

1a 3a 2 29 2 100 98 18±19 (15)

4a 71 ± 50±51 (52)
1b 4b 2 96 2.5 100 97 68±70 (71)
1c 4c 19 97 24 100 96 50±52 (49)
1d 4d 4 96 24 80 76 94±96 (97)
1e 4e 6 97 24 61 58 125±129 (130)

a
Acetophenone (10 mmol), NBS (10 mmol), p-TsOH (1 mmol), methanol (20 ml).
b
All the products were characterized by IR, 1 H NMR and melting points.
c
Time for 100% conversion of 1a±1e.
d
Re¯uxed at 65°C.
e
Isolated yields.
110 M.V. Adhikari, S.D. Samant / Ultrasonics Sonochemistry 9 (2002) 107±111

Scheme 1.

Scheme 2.

in the Scheme 2. The same species can also attack the was achieved in 2 h and a mixture of 3a and 4a in the
aromatic ring. relative ratio of 29:71 was found. As no para substitu-
When the reaction of NBS with acetophenone was tion took place during any of these reactions it can
studied under di€erent conditions (Table 1) the follow- de®nitely be said that there is no radical reaction of NBS
ing observations were made. The reaction of acetophe- possible for this reaction.
none with NBS can be a€ected thermally in the presence As the conversion of 1a increased almost linearly with
of p-TsOH and gave ring-brominated compound only; the quantity of p-TsOH (Table 2) it is clear that the
the yield of m-bromoacetophenone was increased when protonation of NBS is a slow rate-determining step of
temperature was increased. No reaction took place in the reaction (Scheme 1). The quantity of methanol was
the absence of p-TsOH irrespective of the temperature. also found to be a key factor for the reaction (Table 3).
Thus it may be concluded that in the presence of a By increasing the quantity of methanol the conversion
bronsted acid p-TsOH, NBS generates bromocation of 1a was increased.
which is brominating the ring. Polybromo compounds In the case of substituted acetophenones very high
were not formed. selectivity for a-bromination was observed irrespective
As NBS can brominate a suitable substrate through of the substituent present at the para position. It seems
radical reaction [10] the same reaction was done ther- that due to the substituent at the para position the ring
mally in the presence of light. In these reactions only m- bromination at meta position might have gone down.
bromination took place. As compared to the thermal
reactions these reactions are found to be rapid. When
the same reaction was attempted using ultrasound in Acknowledgements
absence of p-TsOH, the reaction did not take place.
However when the sonochemical reaction was carried One of the authors (MVA) is grateful to the G.D.
out in the presence of p-TsOH 100% conversion of 1a Gokhale Charitable Trust, Mumbai for Fellowship. The
 M.V. Adhikari, S.D. Samant / Ultrasonics Sonochemistry 9 (2002) 107±111 111

authors are thankful to Regional Sophisticated Instru- [4] Buu-Hoi, Experientia 2 (1946) 310.
mentation Centre (R.S.I.C.), I.I.T., Mumbai for 1 H [5] P. Bovonsombat, E. McNelis, Synthesis (1993) 237.
[6] V. Paul, A. Sudalai, T. Daniel, K.V. Srinivasan, Synth. Commun.
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[7] W.J. Bailey, J. Bello, J. Org. Chem. 20 (1955) 525.
[8] S.R. Soudagar, S.D. Samant, Ultrason. Sonochem. 2 (1) (1995)
S49.
References [9] S.V. Ley, C.M.R. Low, Ultrasound in Synthesis, Springer, Berlin,
1989.
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