Green halogenation reactions for (hetero)aromatic ring systems in alcohol, water, or no solvent

Article abstract of DOI:10.1139/cjc-2018-0259

A new method of brominating aromatic and heteroaromatic ring systems is investigated. The combination of hydrobromic acid as the halogen source, hydrogen peroxide as the oxidant, and ethanol, water, or no solvent are evaluated as greener conditions than those that have been previously published. The new conditions give high yields and good regioselectivity for a variety of substrates when the ring is activated by electron-donating groups or heteroatoms. Phenols, anisole, thiophenes, and pyrrole give comparable or superior results when compared to a traditional bromination by N-bromosuccinimide in tetrahydrofuran. Other nitrogen-containing heterocycles do not react under the conditions because they are protonated and hence deactivated; similarly, substrates with electron-withdrawing groups are not brominated. The reaction is very tolerant of a variety of functional groups.

Full text of DOI:10.1139/cjc-2018-0259

Page 1 of 18
Green halogenation reactions for (hetero)aromatic
ring systems in alcohol, water, or no solvent
Jessie K. Kajorinne, Jennifer C.M. Steers, Marnie E. Merchant, and Craig D. MacKinnon*
Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario,
P7B 5E1 CANADA;
* corresponding author: Craig D. MacKinnon
telephone: 807-343-8327
fax: 807-346-7775
Kajorinne, JK <<jkkajori@lakeheadu.ca>>
Steers, JCM <<jcsteers@lakeheadu.ca>>
Merchant, ME <<mmercha1@lakeheadu.ca>>
MacKinnon CD <<craig.mackinnon@lakeheadu.ca>>

Page 2 of 18
ABSTRACT: A new method of brominating aromatic and heteroaromatic ring systems is
investigated. The combination of hydrobromic acid as the halogen source; of hydrogen
peroxide as the oxidant; and ethanol, water, or no solvent are evaluated as greener conditions
than those that have been previously published. The new conditions give high yields and good
regioselectivity for a variety of substrates when the ring is activated by electron-donating
groups or heteroatoms. Phenols, anisole, thiophenes, and pyrrole give comparable or superior
results when compared to a traditional bromination by N-bromosuccinimide in tetrahydrofuran.
Other nitrogen-containing heterocycles do not react under the conditions because they are
protonated and hence deactivated; similarly, substrates with electron-withdrawing groups are not
brominated. The reaction is very tolerant of a variety of functional groups.
Keywords
green chemistry
bromination
heterocyclic chemistry
solvent-free synthesis
thiophene

Page 3 of 18
Introduction
Halogenated aromatic compounds are common intermediates in organic synthesis.
Ideally, carbon-carbon bonds can be made directly from hydrocarbons;1 however, as a practical
matter, such reactions are in their infancy, and reactions such as those developed by Stille2 and
Suzuki3 have a wider range of substrates and substitution patterns available to them. Although
both of these reactions require a halogenated substrate and (usually4) an expensive palladium
catalyst to complete the coupling, they continue to be used because of their versatility. In
addition to their synthetic uses, halogenated organics have many commercially important
applications including flame retardants and pesticides.5
Because of this continued need for generating halogenated organic materials,6 focus has
turned to developing more environmentally friendly and sustainable synthetic methods for
generating carbon-halogen bonds. Because of our interest in extended -systems for use as
molecular semiconductors,7-10 we are interested in the halogenation of aromatic rings including
heterocyclic systems, and also require a reaction that has high functional group tolerance.
Thus, we require a source of Br+ to effect electrophilic aromatic substitution. Natural, abundant
sources of the bromine atom are inorganic bromides, so an oxidant is required,11 preferably one
that is not transition metal-based12-14 (including a metal catalyst15) because trace metals can have
a deleterious effect on semiconductor films. Similarly, the oxidant could not be so powerful
that it would react with the substrate, e.g. oxidizing thiophene to S,S-dioxothiophene. Oxone16
and tert-butylhydroperoxide17 were rejected as being atom-uneconomical, while we anticipated
purification difficulties with the high boiling point of dimethylsulfoxide (DMSO) in the
HBr/DMSO system.18,19 A very recent report uses an photo-excited catalytic anthraquinone as
an oxidant, but this adds complexity to the process.20 We therefore chose hydrogen peroxide as

Page 4 of 18
the best oxidant:21-23 it works for both bromination and iodination, it is stable with a variety of
functional groups, it does not oxidize the ring sulfurs in thiophene, and its waste biproduct is
water. Unfortunately, the published peroxide method uses ammonium salts as the halide source
(not atom economical) and acetic acid as solvent (while it can be sustainably sourced, it has a
relatively high boiling point).
To address these issues, we present herein an evaluation of “greener” conditions for
bromination of aromatic24 and heteroaromatic substrates, summarized in Scheme 1.
We
continue to use hydrogen peroxide as the oxidation source, for the reasons given above. Instead
of ammonium bromide, we use hydrobromic acid as the source of Br¯, which saves four atoms
from the ammonium counterion (and reduces the mass by 1/18). Use of HBr has the added
bonus of replacing the acidic proton of acetic acid (rather than using, for example, sodium
bromide25). As a result, solvents that are more sustainable and/or volatile than acetic acid can
be employed, such as ethanol, water, or even elimination of the solvent altogether.26
Experimental Section
Substrates were purchased from Sigma-Aldrich and used as received. Hydrobromic
acid was 48% w/w from Alfa, hydroiodic acid was 47-50% from Baker, hydrogen peroxide was
30% from Fisher. Gas chromatography (GC) was performed on an Agilent 6850 with a
carbowax capillary column and a flame-ionization detector.
Nuclear magnetic resonance
(NMR) spectra were recorded as CDCl3 solutions on a Varian Unity Inova 500 (1H at 500 MHz,
13C at 126 MHz) at room temperature; chemical shifts are reported in ppm referenced to TMS
added to the solvent.

Page 5 of 18
General synthetic procedure (GC-scale). A mixture of 2.0 mmol of substrate and 2.0 or 4.0
mmol of HX were stirred in solvent (if any) for a few minutes. A 30% solution of H2O2 in
water was added in a 10% excess relative to the amount of halogen. The mixture was allowed
to react for 4 hours. At this time, 0.2 mL of the reaction mixture was worked up by adding to
4.0 mL of water and extracted with 4.0 mL of CH2Cl2. The organic layer was separated and
dried with sodium sulfate and the solution injected into the GC. A similar procedure was
performed after 24 hours of total reaction time.
Preparation of 2,5-dibromothiophene (Table 1, entry 13). Thiophene (2.01 g, 23.9 mmol)
and HBr (5.75 mL, 50.7 mmol) were stirred in water while hydrogen peroxide (5.75 mL, 56.3
mmol) was added dropwise over 10 minutes. The mixture was stirred for 24 hours, followed by
extraction in dichloromethane, drying over sodium sulfate, and isolation via rotary evaporation.
Yield 4.58 g (85%, based on 4:1 ratio of C4H2Br2S:C4H3BrS determined by NMR peak
integration). 1H NMR:  6.823 (s, 80% total peak area), 6.858 (dd, J = 5.5 Hz, 4 Hz, 6.7% total
peak area), 7.038 (d, J = 3.5 Hz, 6.7% total peak area), 7.212 (d, J = 5.5 Hz, 6.7% total peak
area) ppm.
Preparation of 2,5-dibromo-3-methylthiophene (Table 2, entry 27).
3-Methylthiophene
(1.00 g, 10.2 mmol) and HBr (2.50 mL, 22.1 mmol) were stirred while hydrogen peroxide (2.50
mL, 24.5 mmol) was added dropwise over 10 minutes. The resultant mixture was stirred for 24
hours, followed by extraction in dichloromethane, drying over sodium sulfate, and isolation via
rotary evaporation. Yield 2.43 g (93%). 1H NMR:  2.128 (s, 3H), 6.734 (s, 1H) ppm.
Preparation of 4-bromoanisole (Table 2, entry 17). Anisole (2.01 g, 19.7 mmol) and HBr
(2.25 mL, 19.9 mmol) were stirred in methanol while hydrogen peroxide (2.25 mL, 22.0 mmol)

Page 6 of 18
was added dropwise over 10 minutes. The resultant mixture was stirred for 24 hours, followed
by extraction in dichloromethane, drying over sodium sulfate, and isolation via rotary
evaporation. Yield 3.18 g (92%). 1H NMR:  3.740 (s, 3H), 6.752 (d, J = 7 Hz, 2H), 7.345 (d,
J = 7 Hz, 2H) ppm.
Preparation of 2-bromo-4-tert-butylphenol (Table 2, entry 13). 4-tert-Butylphenol (1.01 g,
6.7 mmol) and HBr (0.81 mL, 7.2 mmol) were stirred while hydrogen peroxide (0.81 mL, 7.9
mmol) was added dropwise over 10 minutes. The mixture was stirred for 24 hours, followed by
extraction in dichloromethane, drying over sodium sulfate, and isolation via rotary evaporation.
Yield 1.35 g (88%). 1H NMR:  1.266 (s), 6.922 (d, J = 8.5 Hz, 1H), 7.203 (d, J = 8.5 Hz, 1H),
7.446 (s, 1H) ppm.
A small peak (8%) at 7.43 ppm indicates the presence of
2,6-dibromo-4-tert-butylphenol.
Preparation of 2,6-dibromo-4-tert-butylphenol (Table 2, entry 12). 4-tert-Butylthiophene
(1.00 g, 6.67 mmol) and HBr (1.62 mL, 14.3 mmol) were stirred in ethanol while hydrogen
peroxide (1.62 mL, 15.9 mmol) was added dropwise over 10 minutes. The resultant mixture
was stirred for 24 hours, followed by extraction in dichloromethane, drying over sodium sulfate,
and isolation via rotary evaporation. Yield 1.60 g (70%). 1H NMR:  1.268 (s, 9H), 7.427 (s,
2H) ppm.
Results and Discussion
In order to directly compare the new conditions presented herein with the previously
published green syntheses using peroxide in acetic acid,21-23 we chose to look at aromatic
compounds containing benzene and thiophene rings with various substituents. Table 1 gives
results for brominating unsubstituted rings of various types using the mineral acid in the solvents

Page 7 of 18
given; several brominations of the same substrate using N-bromosuccinimide (NBS) in
tetrahydrofuran (THF) are shown for comparison. As can be seen, the alcohols methanol and
ethanol are generally acceptable solvents. On the other hand, reactions done in water are less
successful (with the notable exception of Table 1, entry 13), perhaps due to the fact that the
substrates are not soluble, which gives rise to a two-phase reaction.
In cases where the substrate and brominated product are both liquid, Table 1 also gives
results for “solvent-free” reactions; of course, these are not completely solvent-free because both
the hydrobromic acid and the peroxide are water solutions of 48% and 30% respectively. Neat
reactions are considered the most green, since the solvent is usually the largest single contributor
to the waste stream. Satisfyingly, the no-added-solvent reactions appear to be very successful
in many cases (e.g., Table 1, entry 4; Table 2, entries 18 and 27). Unfortunately, there are
practical difficulties in performing these no-added-solvent reactions, which can easily be
understood in terms of the mechanism. There is general agreement that the reaction of peroxide
with Br¯ generates a Br+ intermediate of the form ROBr,21 e.g., HOBr in water (or CH3OBr in
methanol, CH3COOBr in acetic acid, etc.).
H2O2 + HBr → HOBr + H2O
(1)
However, this net reaction hides the fact that it is a two-step process, i.e.,
2 HBr + H2O2 → Br2 + 2 H2O
Br2 + H2O → HBr + HOBr
(1a)
(1b)

Page 8 of 18
Adding reaction 1a to 1b yields reaction 1. In the case of solvent-free reactions, there is very
little water for soaking up the Br2 (reaction 1b), and we have observed a red haze of gaseous
bromine within the reaction vessels, enough in some cases that metal needles inserted in the
septum to allow pressure equalization are completely destroyed after 24 hours. The strongly
exothermic reaction 1a also causes a rapid temperature rise because there is no solvent to act as a
heat reservoir, which exacerbates the problem by pushing the Br2 into the gas phase. The net
result is that we have found that solvent-free reactions require careful monitering, and even if
that is done, some reactions are not as regioselective under solvent-free conditions (e.g. compare
in Table 1, entries 8 and 11 with entry 15). However, in cases where one product is strongly
favoured, controlled solvent-free reactions will give the same product in similar yield.
Solvent-free reactions where either the substrate or the product is solid gave very poor results in
every case and are not included in the tables.
Having established the stability of the ring systems in the reaction conditions, we next
investigated functional group tolerance. Table 2 displays the results. As is the case with
similar green conditions, electron-withdrawing groups (EWG) prevent bromination, even EWGs
as weak as bromo. The acidic conditions cause protonation of nitrogen groups and rings such
as aniline, thiazole, and pyridine (but not pyrrole), leading to deactivation of the ring and poor
results; the acid-free bromination conditions of Song, et al. work better than our conditions for
nitrogen-containing heterocycles.27 On the other hand, most of these substrates are recovered
unreacted, suggesting that these functionalities are stable, which is promising for the general use
of this reaction on complex molecules. This functional group behaviour is the same as that
observed for the previously-published conditions. The following functional groups are stable in
the reaction conditions: NO2, OH, Br and Cl, CHO, CN, and OCH3; as are the heterocyclic rings

Page 9 of 18
pyridine, thiophene, and thiazole. The benzyl-type methyl group is also stable (Table 2, entries
25 and 27), unlike the HBr-H2O2 oxidation in similar conditions of benzyl to phenylaldyhyde.28
In order to compare the efficacy and regioselectivity of the green conditions, product
distributions were compared to brominations using N-bromosuccinimide (NBS) in
tetrahydrofuran (THF). Besides being atom-uneconomical and using an organic solvent, NBS
reactions have the further disadvantage of succinimide contamination in the resulting product
when a simple workup is used (i.e. no column); this can be seen in the GC of these reactions.
Therefore, our new green conditions are both more atom-economical and less labour intensive
than the equivalent traditional bromination reaction. They are also similar in yield and
regioselectivity to the traditional NBS/THF reactions, for example comparing reactions 8 with 18
and 42 with 45. In a number of cases, the green conditions are considerably better, especially
for benzene (where the THF conditions simply do not work) and phenol (compare Table 2,
entries 2 and 8).
The “GC yields” reported in the Tables are simply the ratios of the GC peaks. Because
the reactions were worked up with an aqueous extraction before injection into the GC, no
water-soluble, involatile, or insoluble biproducts will appear in the chromatograms. Therefore,
for several reactions we performed gram-scale isolation reactions to determine the total amount
of product; the yields are reported under “notes” in Tables 1 and 2 for selected reactions (chosen
from those reactions that were quantitative by GC analysis). We were gratified to find that the
isolated yields were generally high and that product purity (by NMR) is very high, especially
considering that purification was only by extraction, without column chromatography. One
exception was the attempt to scale-up the bromination of neat benzene (Table 1, entry 4), which
resulted in very poor isolated yield. This is perhaps not surprising considering the discussion

Page 10 of 18
above, i.e., that the oxidation reaction is very exothermic and the substrate is volatile – we
conclude that substrate was lost to evaporation as the reaction heated up. The reaction of
thiophene in water (Table 1, entry 13) did not go to completion when scaled up, resulting in a 4:1
ratio of di- to monobromination; the biphasic conditions and the equilibrium between Br2 and
HBr in the presence of water co-conspire to limit the availabilty of Br+, i.e., an excess of
HBr/H2O2 or a longer reaction time would be required to drive this scale-up reaction to
completion.
As expected, chlorides are not accessible under these conditions. This is due to the limit
on the oxidizing power of the peroxide. Unfortunately, iodinations are also not easily done
under these conditions. This was an unpleasant surprise, considering that iodine substitution is
relatively straightforward on activated rings when the solvent is acetic acid22,23 (and in the case
of pyrazoles, water29). Since purple solid collects in the reaction vessel, and since NMR and
GC solutions are coloured purple, it is concluded that while the I¯ is successfully being oxidized
to I2, analogous to reaction 1a, either the subsequent generation of RO-I (reaction 1b) does not
take place or the subsequent iodinization of substrate by RO-I is slow relative to its
comproportionation reaction with I¯ remaining in the solution.
Table 3 shows some
representative data. As can be seen by comparing the same substrates in Tables 1 and 2 with
their entries in Table 3, in cases where bromination occurs quantitatively and regioselectively,
iodination leads to mixtures of products, usually including a significant amount of unreacted
substrate.
Conclusion
We have shown that solvent-free bromination of aromatic and heteroaromatic rings is

Page 11 of 18
possible with the green reagent combination of hydrogen peroxide, bromide, and activated
substrate. The usual issues with solvent-free reactions apply here, viz, the exothermic heat
generation and high concentration gives less selectivity than reactions in solvent and solid
substrates do not work well. Fortunately, in some of these cases, the reaction is often possible
in the solvents methanol, ethanol, or (occasionally) water, which are much greener solvents than
those typically used in bromination reactions. Although these conditions do not appear to be
general to all halogens, working much better for bromine than iodine or chlorine, the reaction
conditions are very forgiving, allowing bromination of a wide variety of ring systems and in the
presence of many different functional groups.
Acknowledgements
Funding for this study was provided by Lakehead University.
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Table 1: Bromination of unsubstituted aromatic rings using various conditions
entry substrate halide
solventa
time
/h
results and reaction selectivityb
source,
halide:
substrate
ratio
unreacted
substrate
mono-Br di-Br
notes
product
product
1
2
benzene
benzene
HBr, 2:1
HBr, 2:1
ethanol
methanol
24
4
0
30
~50
65
trace
5
multiple others
many peaks after
24h
3
4
5
6
7
8
9
benzene
benzene
benzene
benzene
thiophene HBr, 1:1
thiophene HBr, 2:1
thiophene NH4Br,
2:1
HBr, 2:1
HBr, 1:1
HBr, 2:1
NBS, 2:1
water
-
-
THF
ethanol
ethanol
ethanol
24
4
4
24
4
24
120
0
0
0
0
18
0
85
~50
99
99
trace
78
0
trace
0
0
10
4
99
0
multiple others
many products
15
10
11
12
13
thiophene HBr, 1:1
thiophene HBr, 2:1
thiophene HBr, 1:1
thiophene HBr, 2:1
methanol 24
methanol 24
14
trace
0
84
0
36
0
trace
99
64
water
water
24
24
0
99
85% isolated
4:1TBr2:TBrc
14
15
16
17
18
thiophene HBr, 1:1
thiophene HBr, 2:1
thiophene HBr, 3:1
thiophene NBS, 1:1
thiophene NBS, 2:1
-
-
-
4
4
4
4
29
0
0
0
0
42
18
0
91
2
30
82
50
9
also 50% tribromo
THF
THF
24
90
multiple small addn
products
19
20
21
pyrrole
pyrrole
pyrrole
HBr, 1:1
HBr, 2:1
HBr, 1:1
ethanol
ethanol
methanol
4
4
4
6
0
43
82
trace
34
11
99
23
trace tribromo
long rxn time gives
a solidd
22
pyrrole
HBr, 2:1
methanol
4
0
0
63
two higher mass
peaks
23
24
pyrrole
pyrrole
HBr, 1:1
HBr, 1:1
water
-
4
-
0
0
0
0
0
0
solidd
precipitates as
C4H6NBr
25
26
27
28
29
30
pyridine
pyridine
pyridine
furan
furan
furan
HBr, 1:1
HBr, 1:1
HBr, 1:1
HBr, 1:1
HBr, 2:1
HBr, 2:1
ethanol
water
-
ethanol
ethanol
-
24
24
24
4
4
24
100
100
100
0
0
0
0
0
0
0
0
0
0
0
0
35
55
66
no rxn
no rxn
no rxn
many products
many products
many products
5-10%
notes: a “-“ Indicates no solvent. b Relative quantities of residual substrate and product(s) were
determined by peak area integration in GC traces. Calibration was not performed, and detector
response was not calibrated to quantify peak volumes; therefore, GC yields were not determined.
c Relative yield from isolation reaction characterized by NMR peak integrations. d Presumably
a polymerization product

Page 14 of 18
Table 2: Bromination of substituted aromatics and heteroaromatics
entry substrate
halide
source,
substrate:
halide
ratio
solvent time
results and reaction selectivitya
unreacted mono-Br di-Br
notes
substrate
product
product
1
2
3
4
5
6
7
8
9
10
toluene
phenol
phenol
phenol
phenol
phenol
phenol
phenol
phenol
2-Br-phenol
HBr, 1:1 EtOH
HBr, 1:1 EtOH
HBr, 2:1 EtOH
24
4
0
trace
trace
0
many peaks,
incl. benzylb
11
trace
0
65 para
24 ortho
23 para
4
66 (2,4)
2 (2,6)
8 (2,4)
9 tri-Br
HBr, 1:1 MeOH 24
HBr, 2:1 MeOH 24
73 para
18 ortho 1 (2,6)
6 para
0
66 (2,4)
trace 2,6
1 (2,4)
28 tri-Br
HBr, 1:1 water
HBr, 2:1 water
NBS, 1:1 THF
NBS, 2:1 THF
HBr, 1:1 EtOH
24
24
4
25
0
75 para
23 ortho
3 para
86 (2,4
4(2,6)
8 (2,4)
8 tri-Br
39
trace
7
25 para
14 tri-Br
44 tri-Br
12 ortho ~1 (2,6)c
24
24
22 para
trace o
66 (2,4)
10 (2,6)
99
33 (2,4)
~1 (2,6)c
16
11
12
p-tBu-phenol
p-tBu-phenol
HBr, 1:1 EtOH
HBr, 2:1 EtOH
24
24
0
0
0
99
Br,OH orthod
Br,OH ortho
0
70% isolatedd
88% isolatedd
no change after 24h
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
p-tBu-phenol
p-tBu-phenol
p-tBu-phenol
anisole
anisole
anisole
anisole
anisole
anisole
benzaldehyde
nitrobenzene
nitrobenzene
3-MeT
3-MeT
3-MeT
HBr, 1:1 EtOH
NBS, 1:1 THF
NBS, 2:1 THF
HBr, 1:1 EtOH
24
4
24
24
trace
42
0
23
0
7
0
1
0
67
100
100
4
0
0
91
22
8
35
99
trace
77 para
99 para
93 para
30 para
99 para
99 para
33
0
0
96
84
HBr, 1:1 MeOH 24
0
0
70
0
trace
0
0
0
0
15
98
92% isolatedd
HBr, 1:1
HBr, 2:1
-
-
24
24
24
4
24
24
24
4
NBS, 1:1 THF
NBS, 2:1 THF
HBr, 2:1
-
HBr, 1:1 EtOH
HBr, 1:1 water
HBr, 1:1 EtOH
d
HBr, 1:1
HBr, 2:1
-
-
4
24
0
1% tri-Br
93% isolatedd
28
29
30
31
3-MeT
3-MeT
2-TI
2,2’-
NBS, 1:1 THF
NBS, 2:1 THF
4
4
24
24
trace
0
0
99
33
69
22
trace
66
0
HBr, 1:1
-
31% di-Br
10% tri-Br
HBr, 2:1 water
trace
68
bithiophene
1,3-thiazole
thianaphthene
benzofuran
32
33
34
HBr, 1:1 water
HBr, 1:1 EtOH
HBr, 1:1 water
24
20
24
99
46
81
1
54
19
0
0
0

Page 15 of 18
notes: a Relative quantities of residual substrate and product(s) were determined by peak area
integration in GC traces. Calibration was not performed, and detector response was not
calibrated to quantify peak volumes; therefore, GC yields were not determined. b NMR confirms
the presence of benzyl substitution. c This product overlaps with succinimide. d Relative yield
from isolation reaction characterized by NMR peak integrations.

Page 16 of 18
Table 3: Iodination reactions
entry substrate
halide
solvent time
results and reaction
selectivitya
source,
substrate:
halide
unreacted 1:1
2:1
substrate product product
ratio
1
2
3
4
5
6
7
8
benzene
anisole
p-tBu-phenol HI, 2:1
thiophene
thiophene
thiophene
thiophene
thiophene
HI, 2:1
HI, 1:1
EtOH
EtOH
EtOH
EtOH
MeOH 24
water
-
24
24
24
24
100
100
2
0
0
0
0
82
78
0
0
94
87
17
19
58
79
5
HI, 2:1
HI, 2:1
HI, 2:1
HI, 2:1
NIS, 2:1
3
42
21
trace
0
24
24
24
THF
6

Page 17 of 18
Scheme 1
(CH)n
(CH)n
Br
H , H2O2
R
R
EtOH, MeOH, H2O,
or no solvent
Y
H
Y
Br
Y = S or NH, n = 3
or CR', n = 4

Page 18 of 18
Describing greener conditions than previously reported for the bromination of aromatic and
heteroaromatic rings, including a solvent-free option for liquid substrates.
(CH)n
(CH)n
Br
H , H2O2
R
R
EtOH, MeOH, H2O,
or no solvent
Y
H
Y
Br
Y = S or NH, n = 3
or CR', n = 4