Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1097–1099
Visible light induced ‘on water’ benzylic bromination with
N-bromosuccinimide
Ajda Podgorsˇek,a Stojan Stavber,a Marko Zupanb and Jernej Iskraa,*
a‘Jozˇef Stefan’ Institute, Jamova 39, 1000 Ljubljana, Slovenia
bFaculty of Chemistry and Chemical Technology, University of Ljubljana, Asˇkercˇeva 5, Ljubljana, Slovenia
Received 13 October 2005; revised 29 November 2005; accepted 7 December 2005
Available online 27 December 2005
Abstract—Benzylic bromination of various 4-substituted toluenes (Me, tert-Bu, COOEt and COMe) was effectively conducted with
NBS in pure water and with a 40 W incandescent light-bulb as an initiator of the radical chain process, while electron donating
groups (OMe and NHAc) directed the reaction to electrophilic aromatic substitution.
Ó 2005 Elsevier Ltd. All rights reserved.
Although water is a unique solvent for biochemical pro-
cesses, it is traditionally avoided as a medium for organ-
ic reactions.1,2 As demands for ‘greener’ chemistry
increase, attention is being focused on reducing or elim-
inating the use of volatile organic compounds (VOCs),
especially when they are used as solvents. In this case,
the best substitute for VOCs is no solvent at all, but if
a solvent is required then water is preferred (non-toxic,
easily available, inexpensive and non-flammable).3 An
obvious problem when dealing with reactions in aque-
ous media is the solubility of organic molecules. Never-
theless, the group of Sharpless has shown with its ‘on
water’ principle that reactions can be accelerated by
water despite the non-solubility of the reactants.4 Water
is also suitable for radical reactions as it does not inter-
fere with the radical chain process due to its strong OH
bond.5 The well-known Wohl–Ziegler reaction, free radi-
cal benzylic bromination, is traditionally performed with
N-bromosuccinimide (NBS) in boiling carbon tetrachlo-
ride with the addition of a radical initiator.6 The benzyl
bromides thus obtained are valuable chemicals and syn-
thons. Although CCl4 has optimal characteristics for
this reaction, its ozone-depleting ability and increasing
restrictions impelled us to find a system for free radical
bromination with less of an impact on the environment.
So far, research has focused on providing more benign
solvents (e.g., ionic liquids, ethyl or methyl acetate,
and biphasic media)7–9 and different modes of activation
(e.g., light, microwaves, zeolites, and grinding).8,10–12
This report shows that benzylic bromination of hydro-
phobic substrates can be very effectively conducted by
NBS in pure water at ambient temperature and with vis-
ible light as an activator, while the solubility of succin-
imide in water enables easy isolation of the products.
Initially, we wanted to define the best mode of activation
of a radical reaction in water (heat, initiator, and light)
and so conducted a series of reactions with 1 mmol
of 4-tert-butyltoluene 1 and an equimolar amount of
N-bromosuccinimide which were stirred at 500 rpm in
5 mL of water. A blank experiment in the dark afforded
25% conversion of 1 to benzyl bromide 2a despite the
absence of radical-chain initiators (Scheme 1, line 1).
Thermal activation of the radical process (80 °C) was
effective for radical bromination, but 8% of electrophilic
bromination also occurred (Scheme 1, line 2). Next we
activated the radical chain process by adding various
initiators; these included hydrophobic 2,20-azobis(2-
methylpropionitrile) (AIBN), dibenzoyl peroxide
(DBP), and water soluble 4,40-azobis(4-cyanovaleric
acid) (ACVA) and 2,20-azobis(2-methylpropionamidine)
dihydrochloride (AMPA).13 Surprisingly, benzyl bro-
mination was selectively achieved only with non-soluble
AIBN, while DPB and especially both the water soluble
initiators gave a mixture of radical and electrophilic
bromination products (lines 3–6). Finally, we tested a
Keywords: Water; Halogenation; Benzyl bromination; Radical reac-
tions; N-Bromosuccinimide; Aqueous media.
*
Corresponding author. Tel.: +386 14773631; fax: +386 14773822;
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.12.040