3250
G. A. Heropoulos et al. / Tetrahedron Letters 48 (2007) 3247–3250
1964; p 1517; Larock, R. C. Comprehensive Organic
Transformations; VCH: New York, 1989.
was performed with bromine in trimethyl phosphate
and afforded 3-bromo-1,2,4,5-tetrakis(1-ethylpropyl)-
benzene.16
9. (a) General experimental procedures. Commercially avail-
able reagents were used without further purification.
Compounds 12–15 are products of KERAS (keras-
ta@eie.gr). Ultrasound experiments were carried out in a
250 ml sonochemical reaction vessel fitted with a ther-
mometer, a reflux condenser and probe (length 254 mm,
diameter 13 mm) and controlled by a 650 W ultrasonic
processor Sonics and Materials. This processor allows the
ultrasonic vibrations at the probe (titanium alloy) tip to be
set at 90%. The system was operated in the nonpulse
mode. In a typical reaction 0.32 g (3.0 mmol) of p-xylene
and 0.54 g (3.0 mmol) of NBS were sonicated in 15 ml of
water at 90 ꢁC for 40 min. Hexane was added after
sonication and cooling and the whole reaction mixture
was transferred to a separation funnel. The organic layer
was washed three times with 3 · 15 ml of water, dried over
Na2SO4 and analysed by GC and GC–MS. For the NMR
samples the solvent was evaporated prior to analysis. The
comparative thermal reactions were carried out in 15 ml
water at 90 ꢁC for 40 min using the same reagent amounts
as in the ultrasound reactions. The work-up and analysis
of the reaction mixtures was as described above for the
ultrasound assisted reactions; (b) Microwave-promoted
experiments were carried out in the dark with a CEM
Discover 300 W single mode microwave instrument. For
the reactions without water, the closed vessels used were
special glass tubes with self-sealing septa that controlled
pressure with appropriate sensors on the top (outside the
vial). The initial power was 200 W and when the
preselected temperature was obtained it was automatically
adjusted to maintain this temperature. The temperature
was monitored through a non-contact infrared sensor
centrally located beneath the cavity floor. Magnetic
stirring was provided to assure complete mixing of the
reactants. Under these conditions the pressure in the tubes
never exceeded 4 bar. The 10 ml reaction vessels were
charged in air with 0.32 g (3.0 mmol) of o-xylene and
0.54 g (3.0 mmol) of NBS. After the microwave irradiation
was finished, the reaction mixture was cooled rapidly. The
work-up and analysis was as described above for the
ultrasound assisted reactions. When water (15 ml) was
used, the microwave experiments were carried out in a
100 ml round-bottomed three-neck flask equipped with a
magnet and a reflux condenser open to the air. The
reaction vessel was submitted to microwave irradiation for
40 min in the cavity where the power (initially 100 W) was
self-adjusted to maintain 90 ꢁC. The quantities of reagents
were the same as above. When the reaction time was
reached, the mixture was cooled rapidly to rt. Work-up
and analysis was as described above for the ultrasound
assisted reactions.
Br
MW
Br2 (CH3O)3PO
,
46%
We have studied the bromination reaction of various
aromatic compounds with NBS under high-intensity
ultrasound or microwave irradiation with or without
water. From our results it is clear that, in water, ultra-
sound strongly favours ring substitution for aromatic
molecules bearing simple alkyl or hydroxyl groups and
that, in the absence of water, microwaves are selective
for the side-chain bromination of the same molecules.
In the presence of water, the microwave assisted reaction
gives results similar to those using conventional heating
and promotes both ring and side bromination. Further
comparative studies could lead us to predict which
high-energy technique and which conditions should be
used for a given reaction.
Acknowledgements
This investigation was funded by the General Secretariat
of Research and Technology of Greece, by the Marie
Curie Host Fellowships for the Transfer of Knowledge
project ‘Sopholides’ (Contract No. MTKD-CT-2004-
014399) and was carried out under the auspices of COST
Action D32 (WG 006/04) ‘Microwave and high-intensity
ultrasound in the synthesis of fine chemicals’.
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