Poly-N-bromosulfonamide-melamine as a novel brominating reagent for regioselective ipso-bromination of arylboronic acids

Article abstract of DOI:10.1007/s00706-021-02827-2

A practical synthetic method for the synthesis of aryl bromide was developed through regioselective bromination of boronic acid in the presence of poly-N-bromosulfonamide-melamine (PBBSM). In this regard, a novel heterogeneous support, cross-linked poly sulfonamide-melamine, has been successfully synthesized to stabilize bromine with high surface functional group density (6.6?mmol Br⁺/g). The prepared reagent is a novel brominating reagent that combines the effective functions of N-bromosulfonamide, N-bromosulfonamide-melamine, and melamine groups. The structure of PBBSM was characterized using XRD, FT–IR, ¹H NMR, TGA, FE-SEM, EDX, and TGA analysis. Graphic abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-021-02827-2

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-021-02827-2
ORIGINAL PAPER
Poly‑N‑bromosulfonamide‑melamine as a novel brominating reagent
for regioselective ipso‑bromination of arylboronic acids
Sedigheh Alavinia · Ramin Ghorbani‑Vaghei1
1
Received: 12 April 2021 / Accepted: 12 July 2021
©
Springer-Verlag GmbH Austria, part of Springer Nature 2021
Abstract
A practical synthetic method for the synthesis of aryl bromide was developed through regioselective bromination of boronic
acid in the presence of poly-N-bromosulfonamide-melamine (PBBSM). In this regard, a novel heterogeneous support, cross-
linked poly sulfonamide-melamine, has been successfully synthesized to stabilize bromine with high surface functional
+
group density (6.6 mmol Br /g). The prepared reagent is a novel brominating reagent that combines the eꢀective functions
of N-bromosulfonamide, N-bromosulfonamide-melamine, and melamine groups. The structure of PBBSM was characterized
1
using XRD, FT–IR, H NMR, TGA, FE-SEM, EDX, and TGA analysis.
Graphic abstract
B(OH)
2
O
S
Br
BrO
N
O
S
O
Br
N
Br
N
O
S
O
O
S
O
N
N
S
O
Br
O
N
O
N
Regioselective bromination
High to excellent yields
Short reaction time
NBr
n
S
O
Simple operation
Easily accessible SM
Poly-N-bromomelaminesulfonamide (PBBSM)
Heterogeneous reagent
High surface functional group
density (6.6 mmol Br+/g)
Keywords Selective bromination · Poly-N-bromosulfonamide-melamine · Arylboronic acid
Introduction
hazardous oxidizing agents or harsh reaction conditions
4–7]. Recently, boronic acids have gained particular inter-
[
Aryl halides have been regarded as key building blocks in
the ꢁelds of natural product synthesis, drug design, and
organic materials [1, 2]. Recent advances in bromination
chemistry and synthesis of bioactive molecules [3] have led
to the development of eꢀective methods and novel bromi-
nation reagents that selectively form C–Br bond in a safe
manner. C–Br bond formation reactions incarnate the core of
organic synthesis because of their basic applications towards
molecular diversity. Although electrophilic aromatic bro-
mination is still the main procedure for the intended prod-
ucts, the mentioned reactions typically require the use of
est for halodeboronation due to their prevalence in wide
variations, high regioselectivity at the boronic acid position
in comparison to the C–H bromination, stability to air and
moisture, and availability [8, 9]. Deboronation of boronic
acids is considered a promising coupling partner in the syn-
thesis of heterocycles, due to its potency in the formation of a
bond between an aryl ring and a heteroatom after deborona-
tion. The mentioned method can be regarded as an eꢂcient
way of synthesizing (hetero)arene compounds, i.e. arylazides
[10, 11], phenols [12], arylsulfones [13–15], nitroarenes
[16], and aryl halides [17–31]. As compared to other ipso-
substitutions, there are few reports about the ipso-bromina-
tion of boronic acid. In order to synthesize aryl bromides via
bromodeboronation, speciꢁc methods have been suggested
i.e., chloramine-T along with halide ions [25], N-bromosuc-
cinimide [26], 1,3-dihalo-5,5-dimethylhydantoin (DCDMH
*
Ramin Ghorbani-Vaghei
rgvaghei@yahoo.com
1
Faculty of Chemistry, Bu-Ali Sina University,
Hamedan 6517838683, Iran
Vol.:(0
1
123456789)
3

S. Alavinia, R. Ghorbani-Vaghei
or DBDMH) [27], copper-catalyzed halogenation of arylbo-
ronic acids [28], poly(4-vinylpyridine) supported bromine
complexes [29], and electrochemical halodeboronation [30].
It is worth mentioning that some of the brominating reagents
have been reported as being hazardous, toxic, expensive, and
not readily available. Thus, it is very important to prepare
an ideal reagent which is milder, selective, non-hazardous,
and inexpensive.
poly-N-bromosulfonamide-melamine (PBBSM) and a cata-
lytic amount of NaNO (Scheme 1).
2
Results and discussion
PEMA-PSA and PBBSM as heterogeneous reagent was sim-
ply synthesized by one-pot procedure and well-characterized
by XRD, FT–IR, HNMR, TGA, FE-SEM, EDX, and TGA
analysis. The XRD patterns of synthesized PEMA-PSA and
PBBSM are shown in Fig. 1. The diꢀraction peaks in a range
of 2θ angle at about 17.4°, 20°, 21° (due to the melamine
group) [43], 40° and 48° (due to sulfonamide groups) [44]
conꢁrmed the successful formation of the crystal structure
of PEMA-PSA (Fig. 1A). The XRD pattern of PBBSM is
shown in Fig. 1B. The diꢀraction peaks in a range of 2θ
angle 20°, 22.8°, 25° (due to the melamine group), 40°
and 42° (due to sulfonamide groups) were also observed
(Fig. 1B). In addition, after bromination, the overall reduc-
tion in diꢀraction was observed and the texture of polymeric
matric through bromination of PEA-PSA was retained.
In the FT–IR spectrum of the PEMA-PSA, the charac-
The unique properties of porous cross-linked polymers,
including high thermal and chemical stabilities, recyclabil-
ity, large surface area, easy and low-cost production, are the
main reasons for their application in chemical conversion
[
32]. The results obtained from the catalytic application of
sulfonamides indicate that sulfonamides play a vital role in
heterogeneous substrate and catalysts [33–38]. Sulfonamides
have been considered as one of the most important substrates
for stabilizing bromine [39–42]. Continuing our research on
the catalytic application of cross-linked polysulfonamides
[
(
33–38], herein, cross-linked polysulfonamide-melamine
PEMA-PSA) as a new kind of polysulfonamides was syn-
thesized for the immobilization of bromine (Scheme 1).
Although N,N,N’,N’-tetrabromobenzene-1,3-disulfonyla-
mide (TBBDA) has been widely used in the ꢁeld of cata-
lyst, no research has been reported about the cross-linked
polysulfonamide-melamine for the stabilization of bromine.
Continuing our research on the bromination of aromatic
compounds using TBBDA [39–42], we describe a practical
method based on ipso-bromination of boronic acid using
−
1
teristic peak of C=N at 1657 and 1682 cm is attributed
to the melamine groups (Fig. 2A). In the FT–IR spectrum
of the PBBSM, the C=N bonds shifted to lower wavenum-
−
1
ber (1620 and 1628 cm ). In addition, the intensity of
−
1
bands at 3400–3500 cm (NH stretching) was signiꢁcantly
decreased (Fig. 2B).
Scheme 1
1
3

Poly-N-bromosulfonamide-melamine as a novel brominating reagent for regioselective…
related to the physically absorbed water and organic sol-
vents and the mass loss at 350–600 ℃ could be correlated
to the decomposition of polymeric structure and monomers
(
Fig. 4). According to the TGA form, the polymer decom-
poses in one step at 269.45 °C, losing a total of 71.18% of
its weight, and the material decomposes completely after
5
00 °C.
The EDS analysis of PBBSM shows signals of C, O, N, S,
and Br in the structure of PBBSM (Fig. 5). Elemental map-
ping along with EDX analysis conꢁrmed the homogeneous
distribution of the elements (Fig. 6).
The proposed mechanism of this reaction is shown in
Scheme 2. According to this mechanism, ꢁrst, NaNO was
2
reacted with phenylboronic acid to make intermediate A. In
continue, intermediate A underwent electrophilic attack by
+
Br to produce intermediate B. Finally, the desired product
2
a–2l is produced by losing (ONO)–B(OH) [30, 45, 46].
2
The acidity of –NH, which is controlled by the resonance
eꢀect of melamine and SO groups is more than other –NH
2
in the structure of PBBSM, so is more probable to generate
+
a Br .
To investigate the ability of PBBSM reagent to bromo-
deboronation, para-methoxyphenylboronic acid was selected
as the substrate of the model reaction to optimize the reac-
tion conditions (Table 1). The best result was observed when
Fig. 1 XRD pattern of PEMA-PSA (A), PBBSM (B)
0
.3 g of PBBMS was employed giving 2k in 74% yield
(
entry 2). In addition, more amount of PBBSM led to the
decreased product yields (entry 3). Afterwards, the eꢀect
of NaNO along with PBBSM on the reaction progress was
2
examined (entries 4, 5). According to Table 1, the optimal
catalyst of NaNO was found to be 0.5 mmol to push the
2
reaction forward (entry 4). As per catalytic results in dif-
ferent solvents (entries 4–11), CH CN gave the best results
3
(
entry 4). While studying the eꢀect of temperature (entries
6
–8), the best result was observed at 80 °C (entry 12 vs.
entry 4). Under the optimal conditions, a group of arylbo-
ronic acids was selected to examine the substrate scope for
this conversion (Table 2). PBBSM/NaNO provided the
2
ipso-brominated products in high to excellent yields for a
wide range of functional groups on phenylboronic acids.
With regard to the scope of boronic acids, both electron-
withdrawing (2b–2i) and electron-donating (2j–2l) substi-
tuted arylboronic acids are all good substrates. Interestingly,
electron-donating substrates was found to react at a much
higher rate as compared to electron-withdrawing substrates
(entries 11 vs. 6, 8, 9). That could be explained on the basis
of more available electron density of boronic acid group.
According to the literature, to synthesize 1-bromo-3-ni-
trobenzene from m-nitroboronic acid via bromodeboronation
Fig. 2 The FT–IR spectra of PEMA-PSA (A), PBBSM (B)
FE-SEM images of PEMA-PSA (Fig. 3A) and PBBSM
(
Fig. 3B) show a signiꢁcant change in the surface morphol-
ogy of PBBSM as compared to that of PEMA-PSA. Moreo-
ver, the surface roughness of polymer increases. The sam-
ples indicate a 3D porous network with multiple spherical
nanopores.
NBS, PVP-Br reagents, and electrochemical conditions can
2
To investigate the thermal stability of PBBSM, thermal
gravimetric analysis was conducted and the outcome is
depicted in Fig. 4. A small loss weight at 100 ℃ could be
be applied (Table 3). The present study clariꢁes the fact that
applying PBBSM would signiꢁcantly shorten the reaction time
and enhance the yield (entry 4). The surface density of the Br+
1
3

S. Alavinia, R. Ghorbani-Vaghei
Fig. 3 FE-SEM images of
PEMA-PSA (A), PBBSM (B)
Fig. 4 TGA curve of PBBMS
groups was determined using the back titration method. A high
of PBBSM have been clariꢁed that the reagent is a stable,
low-toxic, heterogeneous, and easily handled solid. Moreo-
ver, other functional groups which are available in the aro-
matic ring of the substrates are not damaged. The results
illustrate that the high loading results in the high perfor-
mance of the PBBSM for the synthesis of bromobenzenes.
Hence, because of these great features, we would like to
recommend PBBSM as a robust and promising candidate
for this signiꢁcant type of chemical conversion.
+
surface density functional group (6.6 mmol Br /g) leads to
high selectivity and eꢂciency of the products.
Conclusion
In summary, we propose a novel brominating reagent
for ipso-bromination of the activated and deactivated
boronic acids in the presence of NaNO . The advantages
2
1
3

Poly-N-bromosulfonamide-melamine as a novel brominating reagent for regioselective…
Fig. 5 EDX spectrum of
PBBSM
Fig. 6 Elemental mapping of
PBBSM
1
3

S. Alavinia, R. Ghorbani-Vaghei
Scheme 2
Experimental
DIAMOND instrument. The qualitative analysis of PBBSM
was performed by using energy-dispersive X-ray spectroscopy
(EDS). Scanning electron microscopy (SEM) was performed
on EM3200 instrument operated at 30 kV accelerating volt-
age. Wavelength-dispersive X-ray spectroscopy (WDX) was
performed using a TESCAN mira3. XRD measurements were
carried out on X-ray diꢀractometer (Panalytical X Pert Pro)
equipped with a CuKα radiation (λ=1.54060 Å) operated at
a voltage of 45 kV and current 40 mA.
All commercially available chemicals were obtained from
Merck and Fluka companies and used without further puriꢁ-
cation otherwise stated. Nuclear magnetic resonance (NMR)
spectra were recorded in DMSO on Bruker Avance spectrom-
1
eters 250 MHz and 500 MHz for H NMR using TMS as
an internal standard; chemical shifts were expressed in parts
per million (ppm). Mass spectra were recorded on a Shi-
madzu QP 1100 BX Mass Spectrometer. Melting points were
determined on a Stuart Scientiꢁc SMP3 apparatus. Thermo-
gravimetric analysis (TGA) was performed on a PYRIS
Table 2 Regioselective bromination of boronic acid using PBBSM/
NaNO
2
Table 1 Optimizing of the reaction conditions
Entry
R
Producta
Time
/h
Yieldb
/%
a
Entry
PBBSM NaNO
Time
/h
T
/°C
Solvent
Yield
/%
2
/g
/mmol
1
2
3
4
5
6
7
8
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
2
1
1
1
1
2
1
2
2
2
1
1
85
81
85
92
70
94
90
85
88
78
94
87
1
2
3
4
5
6
7
8
9
0.2
0.3
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0
0
0
0.5
1
0.5
0.5
0.5
0.5
0.5
0.5
3
3
3
1
1
2
2
2
3
3
3
80
80
80
80
80
80
80
80
80
80
80
CH CN
65
74
72
94
94
42
64
80
32
37
59
p-COCH3
p-CHO
p-Cl
p-COOH
p-Br
3
CH CN
3
CH CN
3
CH CN
3
CH CN
3
H O
p-F
2
EtOH
DMF
DCM
m-NO2
p-NO2
p-OH
p-OMe
p-Me
9
10
11
12
2j
2k
2l
10
1
Toluene
1
Solvent-
free
Reaction conditions: boronic acid derivatives (2 mmol), 0.3 g
1
2
0.3
0.5
1
60
CH CN
82
3
3
PBBSM, NaNO (0.5 mmol), and 2 cm CH CN at 80 °C (sealed
2
3
tube)
Reaction conditions: boronic acid (2 mmol), 0.3 g PBBSM, NaNO
2
3
a
(
0.5 mmol), 2 cm CH CN, temperature and time indicated in the
Products were characterized by their physical properties, comparison
3
table
with authentic samples
a
b
Isolated yield
Isolated yield
1
3

Poly-N-bromosulfonamide-melamine as a novel brominating reagent for regioselective…
Table 3 Comparison of the present methodology with some reported methods for the synthesis of 1-bromo-3-nitrobenzene
Entry Conditions
Yield /% [Ref]
1
2
m-Nitroboronic acid (1 mmol), NBS (2 eq), CH CN, 80 ℃, 24 h
19 [26]
82 [30]
3
m-Nitroboronic acid (0.2 mmol), NaBr (1.2 eq), n-Bu NOAc (1 eq), CH OH in an undivided cell with a C(+)/Glassy
4
3
C(−) electrode pairs, 40 °C, 4 h
3
4
m-Nitroboronic acid (1 eq), PVP-Br (1.35 eq), NaNO (0.25 eq), CH CN, 80 ℃, 50 h
78 [29]
2
2
3
m-Nitroboronic acid (2 mmol), PBBSM (0.3 g), NaNO (0.5 mmol), CH CN. The vial was sealed and heated at 80 ℃ for 85 [This work]
2
3
2
h
5
6
.
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3
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1
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4
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Acknowledgements We are thankful to Bu-Ali Sina University, Center
of Excellence in Development of Environmentally Friendly Methods
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