Efficient Synthesis of Bis(dibromomethyl)arenes as Important Precursors of Synthetically Useful Dialdehydes

Article abstract of DOI:10.1055/s-0035-1561651

This work presents an efficient synthesis of bis(dibromomethyl)benzenes and a bis(dibromomethyl)thiophene as precursors of aromatic dialdehydes by bromination of dimethyl-substituted arenes under various reaction conditions (yields up to 99%). Several new variants of this reaction, including the use of N-bromosuccinimide (NBS) and bromine, and various solvents to replace carbon tetrachloride, benzene and carbon disulfide, were also tested. In the optimised protocols, the inconvenient solvents were replaced by 1,2-dichloroethane (DCE) and/or acetonitrile. In the DCE protocols, we reduced reaction times 24-32-fold, reduced the amount of NBS a fewfold and lowered power consumption relative to the literature protocols. The procedures also allowed elimination of long-lasting incandescent irradiation (100-500 W). The replacement of NBS by bromine led to a further reduction in the amount of brominating agent. The obtained bromo derivatives were efficiently converted into the corresponding dialdehydes (90-96%), which in turn are useful in materials chemistry.

Full text of DOI:10.1055/s-0035-1561651

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–F
paper
A
A. Bodzioch et al.
Paper
Synthesis
Efficient Synthesis of Bis(dibromomethyl)arenes as Important
Precursors of Synthetically Useful Dialdehydes
Agnieszka Bodzioch*a
Br
Br
Krzysztof Owsianika
Joanna Skalika
Emilia Kowalskaa
Anna Stasiaka
Ewa Różycka-Sokołowskab
Bernard Marciniakb
Piotr Bałczewski*a,b
CHO
R2
Me
R2
OHC
R1
Me
R1
AgNO3
[Br]
Br
Br
Ar
Ar
Ar
DCE or MeCN
various
conditions
EtOH/H2O
R1
R2
90–96%
87–99%
4 examples
[Br] = NBS, Br2
a Department of Heteroorganic Chemistry, Centre of Molecular and
Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza
112, 90-363 Łódź, Poland
b Jan Długosz University in Częstochowa, Institute of Chemistry, Envi-
ronmental Protection and Biotechnology, The Faculty of Mathemat-
ics and Natural Sciences, Armii Krajowej 13/15, 42-201 Częstochowa,
Poland
agabodz@interia.pl
pbalczew@cbmm.lodz.pl
Received: 15.04.2016
Accepted after revision: 27.04.2016
Published online: 09.06.2016
The dibromination of methyl groups in arenes is a
known process;1a–c however, the reaction procedures are of-
ten inconvenient and have not been optimised. They usual-
ly require long reaction times in refluxing, toxic solvents
(CCl4, benzene, CS2), use of a large excess of non-optimised
amounts of brominating agents, and long-lasting UV or in-
candescent irradiation that leads to high power consump-
tion. The aromatic dialdehydes 3 constitute useful com-
pounds for the preparation of more complex molecules,
which have been successfully used as optoelectronic mate-
rials, such as dibenz[a,j]anthracene,1a 2,3,6,7-tetraphe-
DOI: 10.1055/s-0035-1561651; Art ID: ss-2016-t0256-op
Abstract This work presents an efficient synthesis of bis(dibro-
momethyl)benzenes and a bis(dibromomethyl)thiophene as precursors
of aromatic dialdehydes by bromination of dimethyl-substituted arenes
under various reaction conditions (yields up to 99%). Several new vari-
ants of this reaction, including the use of N-bromosuccinimide (NBS)
and bromine, and various solvents to replace carbon tetrachloride, ben-
zene and carbon disulfide, were also tested. In the optimised protocols,
the inconvenient solvents were replaced by 1,2-dichloroethane (DCE)
and/or acetonitrile. In the DCE protocols, we reduced reaction times
24–32-fold, reduced the amount of NBS a fewfold and lowered power
consumption relative to the literature protocols. The procedures also al-
lowed elimination of long-lasting incandescent irradiation (100–
500 W). The replacement of NBS by bromine led to a further reduction
in the amount of brominating agent. The obtained bromo derivatives
were efficiently converted into the corresponding dialdehydes (90–
96%), which in turn are useful in materials chemistry.
nylanthracene,2
dibenzo[d,d′]benzo[1,2-a:4,5-a′]dicyclo-
heptenes1b and poly(p-phenylenevinylene) derivatives.3 Di-
aldehydes 3 have also been applied in the synthesis of
spindle-type chromophores for nonlinear, optical materi-
als4,5 and dithienothiophene-based polymers as promising
materials for electrochromic displays and inks.6 Both dibro-
modialdehyde isomers 3a and 3b have very recently been
applied by our group in the synthesis of positional isomers
of higher analogues of o-bromo(hetero)acenaldehydes.7 Bi-
ological applications of dialdehydes 3 include the synthesis
of cephalostatin analogues8 and an o-quinone derivative of
benzo[a]pyrene as an active carcinogenic metabolite of the
parent polycyclic aromatic hydrocarbons.9
Key words bis(dibromination), dialdehydes, radical reaction, solvents,
bromine, N-bromosuccinimide
The aim of our present research was the synthesis of
bis(dibromomethyl)aromatic derivatives 2 and aromatic di-
aldehydes 3, as precursors of more complex, π-conjugated
compounds, useful as optoelectronic materials. Isomeric di-
bromoxylenes 1a and 1b, monobromoxylene 1c and 2,5-di-
methylthiophene (1d) represent substrates for the corre-
sponding bis(dibromomethyl)benzenes 2a–c and 3,4-dibro-
mo-2,5-bis(dibromomethyl)thiophene (2d) which can be
further hydrolysed to the corresponding aromatic dialde-
hydes 3 with an aqueous ethanolic solution of silver nitrate
(Scheme 1).
Synthesis of the precursor bis(dibromomethyl)benzenes
2a–c has been limited to two methods involving perbromi-
nation of single isomers of the corresponding dibromox-
ylene 1a and bromoxylene 1c with N-bromosuccinimide
(NBS) and dibromoxylene 1b with bromine.1a–c,8,10 Thus,
bis(dibromination) of 1a with a large excess (19 equiv) of
NBS in refluxing carbon tetrachloride for 9 hours under in-
candescent irradiation (100 W) gave the desired 1,5-dibro-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

B
A. Bodzioch et al.
Paper
Synthesis
Br
Br
CHO
R2
Me
R2
OHC
R1
Me
R1
AgNO3
Br2 or NBS
Br
Br
Ar
Ar
Ar
EtOH/H2O
DCE or MeCN
R1
R2
1
2
3
R1, R2 = Br, H, Me
Br
Me
Me
Br
Me
Br
Me
Me
Me
1:
Me
S
Br
Br
Me
a
b
c
d
Scheme 1 Bis(dibromination) of methyl groups in arenes 1
mo-2,4-bis(dibromomethyl)benzene (2a) in 88% yield.1a
The bis(dibromination) reaction of 1,4-dibromo-2,5-di-
methylbenzene (1b) with bromine in refluxing carbon tet-
rachloride, under irradiation with a high-power 500 W in-
candescent lamp for 4 hours, gave 1,4-dibromo-2,5-bis(di-
bromomethyl)benzene (2b) in 89% yield.1b Synthesis of 2-
bromo-1,3-bis(dibromomethyl)benezene (2c) required
conducting the reaction with 12 equivalents of NBS in re-
fluxing benzene and incandescent irradiation for an ex-
tended 8 days.8,10 On the other hand, bis(dibromination) of
1a in refluxing carbon tetrachloride was achieved using
only 4 equivalents of NBS.1c Bromination of 2,5-dimethyl-
thiophene (1d) with bromine in the inconvenient solvent
carbon disulfide afforded 3,4-dibromo-2,5-bis(dibro-
momethyl)thiophene (2d) in 71% yield.1d
In our studies, we optimised reaction conditions for the
bromination of 1 in solvents other than carbon tetrachlo-
ride (bp 76.7 °C) (Scheme 1). It turned out that acetonitrile
(bp 82 °C), considered as a preferred and usable solvent in
the Pfizer solvent selection guide,11 worked well in the case
of isomeric 1a and 1b. In other cases, acetonitrile resulted
in failure and only 1,2-dichloroethane (DCE) gave high
yields of the final brominated products. As brominating
agents, we used NBS and bromine. In the case of NBS, sol-
vents (such as DCE, MeCN and benzene) in the presence or
absence of radical initiators could be employed. We first at-
tempted the bromination reaction of 1a and 1b in benzene
to achieve only 65% and 81% yield of 2a and 2b, respectively
(Table 1, entry 1, and Table 2, entry 2; see also Supporting
Information).
ter 6 hours, 4 in 44% and 2a in only 56% NMR yield. Prolon-
gation of the reaction time to 12 hours resulted in an in-
creased NMR yield of the tetrabrominated product 2a to
70% (see Table S1 in Supporting Information). Finally, the
full conversion of 1a into 2a was achieved using 8 equiva-
lents of NBS within 4.5 hours (Table 1, entry 3). The same
reaction conditions were applied to the synthesis of the
second isomer, 1,4-dibromo-2,5-bis(dibromomethyl)ben-
zene (2b), which was obtained in high yield (94%) by the re-
action of 1,4-dibromo-2,5-dimethylbenzene (1b) with 8
equivalents of NBS in refluxing DCE and in the presence of
benzoyl peroxide (Table 2, entry 3). Bromination of isomers
1a and 1b with NBS in refluxing acetonitrile11 in the pres-
ence of benzoyl peroxide provided 2a and 2b in almost
quantitative yields (Tables 1 and 2, entry 4); however, both
reactions required use of the optimised 14 equivalents of
Table 1 Optimisation of the Bromination of 1a
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
conditions
Br
Br
2a
4
Br
Br
1a
Br
Br
5
Entry
Reaction conditions
Yield (%) Yield (%) Yield (%)
of 2a
of 4
of 5
In our next attempts, we applied DCE as a solvent and
benzoyl peroxide as a radical initiator. Surprisingly, follow-
ing the literature procedure12 of refluxing 1a with 3 equiva-
lents of NBS for 2.5 hours, we obtained mainly 1,5-dibro-
mo-2-(bromomethyl)-4-(dibromomethyl)benzene (4) (so
far unknown) instead of the expected 1,5-dibromo-2,4-
bis(bromomethyl)benzene (5). After 5.5 hours, an addition-
al product appeared on TLC, which was identified by 1H
NMR spectroscopy as 1,5-dibromo-2,4-bis(dibromometh-
yl)benzene (2a) (see Table S1 in Supporting Information).
Further increase in the amount of NBS (6.5 equiv) gave, af-
1
2
3
4
5
NBS (12 equiv), AIBN, benzene,
100 W lamp, reflux, 6 d
65
0
12
NBS (3 equiv), benzoyl peroxide,
DCE, reflux, 5.5 h
6a
57a
0
37a
0
NBS (8 equiv), benzoyl peroxide,
DCE, reflux, 4.5 h
97
96
87
NBS (14 equiv), benzoyl peroxide,
MeCN, reflux, 16 h
0
0
Br2 (5 equiv), DCE, 100 W lamp,
reflux, 8 h
0
0
a Yield based on 1H NMR spectra.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

C
A. Bodzioch et al.
Paper
Synthesis
NBS and prolongation of the reaction time to 15–16 hours.
Bromination of xylene derivatives 1a and 1b carried out in
acetone, methanol and alkyl acetates13 did not proceed.
Bromination of 1b according to the literature protocol13a
with NBS (4.4 equiv) and AIBN (4 mol%) in refluxing ethyl
acetate using a 100 W incandescent lamp for 16 hours led to
symmetrical dibrominated product 6 only. Further increase
in the amount of NBS to 8.8 equivalents and the reaction
time to 48 hours did not lead to formation of the bis(dibro-
minated) product 2b. Instead, a competitive α-keto bromi-
nation of ethyl acetate with bromine occurred.
Br
Br
Br
Br
AgNO3
Br
Br
O
O
EtOH/H2O, reflux
S
S
Br
Br
2d
3d (94%)
Scheme 3 Synthesis of 3,4-dibromo-2,5-thiophenedicarbaldehyde
(3d) from 2d
Bromination of 2,5-dimethylthiophene (1d) with bro-
mine (5 equiv) in refluxing DCE for 16 hours afforded 3,4-
dibromo-2,5-bis(dibromomethyl)thiophene (2d) accompa-
nied by 3,4-dibromo-2,5-bis(bromomethyl)thiophene (7)
(Table 3, entry 1).14 Only the application of an additional 2.5
equivalents of bromine resulted in the formation of the de-
sired 2d in almost quantitative yield after 32 hours (Table 3,
entry 2). Notably, the bromination of 1d with 7 equivalents
of bromine in dichloromethane for 18 hours without irradi-
ation did not afford the expected hexabrominated product
2d, but only tetrabrominated 7 in 88% yield.14
Table 2 Optimisation of the Bromination of 1b
Br
Br
Br
Br
Br
Br
Br
conditions
Br
Br
Br
Br
Br
1b
2b
6
Entry Reaction conditions
Yield (%) Yield (%)
of 2b
of 6
1
2
NBS (8 equiv), AIBN, benzene, reflux, 18 d
80
81
11
0
Table 3 Optimisation of the Bromination of 1d
NBS (8 equiv), AIBN, benzene, 100 W lamp,
reflux, 4 d
Br
Br
Br
Br
conditions
3
4
5
NBS (8 equiv), benzoyl peroxide, DCE, reflux,
4 h
94
0
0
0
Br
Br
Br
Br
S
S
S
Br
Br
NBS (14 equiv), benzoyl peroxide, MeCN, reflux, 95
15 h
1d
2d
7
Br2 (5 equiv), DCE, 100 W lamp, reflux, 4 h
93
Entry Reaction conditions
Yield (%) Yield (%)
of 2d
of 7
1
2
Br2 (5 equiv), DCE, 100 W lamp, reflux, 16 h
Br2 (7.5 equiv), DCE, 100 W lamp, reflux, 32 h
35
99
65
0
Alternatively, we used bromine in DCE for the synthesis
of bis(dibrominated) products 2 from dimethylbenzenes
1a–c and dimethylthiophene 1d. Thus, bromination of 1a
with bromine in boiling DCE, supported by a 100 W incan-
descent lamp, gave 2a in 87% isolated yield (Table 1, entry
5). The same reaction conditions applied to the more reac-
tive isomer 1b afforded 2b in 93% yield within 4 hours
(Lit.1b 500 W, 89% yield) (Table 2, entry 5).
Summing up our results on the bromination of dimeth-
ylarenes, we noticed that the efficiency of bromination de-
pended on the kind and amount of brominating agent. Even
under the optimised reaction conditions, we had to use
larger amounts of NBS than bromine.
Synthesis of 2-bromo-1,3-bis(dibromomethyl)benzene
(2c) has been realised by reaction of 2-bromo-1,3-dimeth-
ylbenzene (1c) with bromine (Scheme 2). In contrast to the
literature, this reaction in DCE gave 2c in high yield (93%) in
a short reaction time (2 h instead of 8 d10) and allowed
avoidance of a large excess (12 equiv) of brominating agent
(NBS).8,10 On the other hand, the same reaction in acetoni-
trile, instead of DCE, did not provide the desired product 2c.
The final step of the synthesis required the conversion
of bromides 2 into the corresponding dialdehydes 3
(Scheme 1). We applied the literature procedure which in-
volves hydrolysis of a dibromomethyl moiety to an alde-
hyde group with an aqueous ethanolic solution of silver ni-
trate. In the case of 2a–c, we obtained the dialdehydes 3a–c
in yields which were comparable to those reported in the
literature (93–94%).1a,b,8 3,4-Dibromo-2,5-thiophenedicar-
baldehyde (3d) was obtained from 2d in the same manner,
in 94% yield (Scheme 3). The direct 2,5-diformylation of the
corresponding 2,5-dilithiothiophene with N-formylpiperi-
dine provided 3d in only 54–80% yield.9,15
Br
Br
Br
Br
Br2 (5 equiv), 100 W lamp
DCE, reflux, 2 h
Me
Me
Br
Br
1c
2c (93%)
X-ray crystal structure analysis was performed at room
temperature for crystals of two final products, namely dial-
dehydes 3a and 3b, and of one of the starting materials,
namely 1b (Figure 1). The structural assignment based on
Scheme 2 Bromination of 2-bromo-1,3-dimethylbenzene (1c)
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

D
A. Bodzioch et al.
Paper
Synthesis
X-ray analysis, carried out by us for the first time, for a crys-
tal of 3a shows that this compound crystallises in the
monoclinic P21/c space group with one symmetry-indepen-
dent, practically planar molecule (Figure 1, c) in the unit
cell. In the crystal structure the molecules are connected by
the C3–H3···O2i hydrogen bond [C3–H3 = 0.93 Å, H3···O2 =
2.41 Å, C3···O2 = 3.319(9) Å and C3–H3···O2 = 167°, symme-
try code (i) 1 + x, y, –1 + z] into a simple C(6) chain. Two such
chains are linked by a halogen···halogen interaction of type I
consumption using optimised amounts of N-bromosuccin-
imide. The replacement of NBS by bromine allowed a fur-
ther reduction in the amount of brominating agent. Alter-
native procedures using the preferable acetonitrile only
worked well for the formation of 2a and 2b. All presented
protocols enable efficient syntheses of aromatic dialde-
hydes 3 as substrates for biologically active compounds and
materials for optoelectronic devices.
[i.e., C4–Br2···Br2ii, Br2···Br2 = 3.591(1) Å, C4–Br2···Br2ii
=
C4ii–Br2ii···Br2 = 139.31°, symmetry code (ii) 2 – x, –y, –z], so
generating a one-dimensional framework in the form of an
infinite tape built up from rings consisting of 18 atoms (Fig-
ure 1, d). There are no directional interactions between the
molecules of adjacent tapes. This may be because the sub-
stituents at positions 1 (formyl group) and 2 (Br atom) do
not participate in the formation of these interactions.
1H NMR (500 or 200 MHz) and 13C NMR (125 or 50 MHz) spectra were
recorded with a Bruker AV-III-500 or a Bruker AV-200 spectrometer.
IR spectra were recorded with an ATI Mattson Infinity FTIR 60 spec-
trophotometer. The mass spectra of pure compounds were obtained
using a Finnigan MAT 95 spectrometer. Melting points were deter-
mined using a Boetius apparatus. Column chromatography was per-
formed on Merck silica gel 60 (F254, 270–400 mesh).
General Procedures for the Synthesis of 2a and 2b
Variant A (NBS, Acetonitrile)
To a stirred solution of dibromodimethylbenzene 1a or 1b (3.33 g,
12.6 mmol) in MeCN (120 mL), benzoyl peroxide (65 mg, 0.26 mmol)
and NBS (17.9 g, 100.8 mmol) were added in a single portion. The
mixture was heated to reflux and an additional portion of benzoyl
peroxide (184 mg, 0.74 mmol) was added. The reaction mixture was
stirred at reflux for 8 h, then an additional portion of NBS (13.4 g) was
added and reflux was continued for 8 h. After cooling, the precipitat-
ed solids were filtered off and rinsed with hexane (150 mL). The com-
bined filtrates were concentrated under reduced pressure and puri-
fied by flash column chromatography (petroleum ether) to give 2a
(6.99 g, 96% yield) or 2b (6.84 g, 95% yield).
Variant B (NBS, 1,2-Dichloroethane)
To a stirred solution of dibromodimethylbenzene 1a or 1b (3.25 g,
12.3 mmol) in DCE (120 mL), benzoyl peroxide (63 mg, 0.26 mmol)
and NBS (17.5 g, 98.4 mmol) were added in a single portion. The mix-
ture was heated to reflux and an additional portion of benzoyl perox-
ide (180 mg, 0.74 mmol) was added. The reaction mixture was stirred
at reflux for 4.5 h and then cooled to room temperature. The precipi-
tated solids were filtered off and rinsed with hexane (150 mL). The
combined filtrates were concentrated under reduced pressure and
purified by flash column chromatography (petroleum ether) to give
2a (6.94 g, 97% yield) or 2b (6.7 g, 94%).
Figure 1 Views of molecules of 1b (a), 3b (b) and 3a (c) with the
atom-numbering scheme and displacement ellipsoids drawn at the 30%
probability level; black dashed lines depict the intramolecular C–H···Br
hydrogen bonds. (d) Part of the crystal structure of 3a showing the C–
H···O and Br···Br interactions (red and green dashed lines, respectively)
linking the molecules into a tape built up from 18-membered rings.
Variant C (Br2, 1,2-Dichloroethane, Light)
Dibromodimethylbenzene 1a or 1b (3.76 g, 14 mmol) was dissolved
in DCE (40 mL) under reflux and then Br2 (10.9 g, 3.5 mL, 71 mmol)
was added dropwise to the solution. The resulting mixture was re-
fluxed under incandescent irradiation (100 W) for 8 h (for 1a) or 4 h
(for 1b). After cooling to room temperature, the reaction mixture was
quenched with an aqueous solution of NaHSO3. The organic layer was
dried over MgSO4 and evaporated to dryness to give 2a (7.06 g, 87%
yield) or 2b (7.55 g, 93% yield).
In conclusion, we have presented optimised and effi-
cient protocols for the preparation of bis(dibromomethyl)-
substituted arenes 2 as synthetically useful precursors of
the corresponding dialdehydes 3. In the syntheses, we re-
placed inconvenient carbon tetrachloride, benzene and car-
bon disulfide by DCE, which allowed an efficient synthesis
of 2. Compared to the literature methods, we obtained the
desired products 2a–d in higher yields (up to 99%), in much
shorter reaction times (hours versus days) and lower power
1,5-Dibromo-2,4-bis(dibromomethyl)benzene (2a)
White solid; mp 122–123 °C (from hexane) (Lit.1a 115–118 °C).
IR (KBr): 3434, 3083, 3024, 3014, 1582, 1541, 1452, 1423, 1366, 1255,
1148, 1050, 980, 899, 868, 769, 719, 689, 654, 618, 594, 554 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

E
A. Bodzioch et al.
Paper
Synthesis
1H NMR (500 MHz, CDCl3): δ = 8.66 (s, 1 H, ArH), 7.70 (s, 1 H, ArH),
6.96 (s, 2 H, CHBr2).
13C NMR (125 MHz, CDCl3): δ = 141.2, 135.7, 133.5, 121.2, 37.7.
HRMS (EI): m/z [M]+ calcd for C8H4Br6: 573.54139; found: 573.54176.
Anal. Calcd for C8H4Br6: C, 16.58; H, 0.70. Found: C, 16.71; H, 0.67.
descent irradiation (100 W) for 16 h. Then, an additional amount of
Br2 (3.55 g, 1.14 mL, 22.3 mmol) was added and refluxing was contin-
ued for 16 h. After cooling to room temperature, the reaction mixture
was quenched with an aqueous solution of NaHSO3. The organic layer
was dried over MgSO4 and evaporated to dryness to give 2d (5.17 g,
99% yield) as a light yellow solid.
IR (KBr): 2980, 1318, 1186, 1162, 1122, 870, 784, 685, 631 cm–1
1H NMR (200 MHz, CDCl3): δ = 6.91 (s, CHBr2).
13C NMR (50 MHz, CDCl3): δ = 143.3, 112.5, 30.2.
HRMS (EI): m/z [M]+ calcd for C6H2SBr6: 579.49781; found:
579.49858.
.
1,4-Dibromo-2,5-bis(dibromomethyl)benzene (2b)
White solid; mp 168–170 °C (from hexane) (Lit.1b 176–178 °C).
IR (KBr): 3434, 3011, 1646, 1359, 1287, 1216, 1153, 1058, 893, 807,
700, 661, 554 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.13 (s, 2 H, ArH), 6.93 (s, 2 H, CHBr2).
13C NMR (125 MHz, CDCl3): δ = 143.8, 135.8, 120.3, 38.0.
HRMS (EI): m/z [M]+ calcd for C8H4Br6: 573.54139; found: 573.54065.
Anal. Calcd for C6H2SBr6: C, 12.31; H, 0.34; S, 5.48. Found: C, 12.43; H,
0.32; S, 5.19.
3,4-Dibromo-2,5-thiophenedicarbaldehyde (3d)
Anal. Calcd for C8H4Br6: C, 16.58; H, 0.70. Found: C, 16.75; H, 0.72.
To a solution of 2d (302 mg, 0.516 mmol) in EtOH (10 mL) was added
a solution of AgNO3 (369 mg, 2.17 mmol) in water (4 mL). The result-
ing mixture was heated at reflux under argon for 40 min. The solution
was allowed to cool; AgBr was filtered off and washed with EtOH
(2 × 5 mL). The solvent was evaporated and the residue was purified
by recrystallisation (from hexane) to give 3d (146 mg, 94% yield) as a
white solid; mp 230–231 °C (from EtOH).
1,5-Dibromo-2-(bromomethyl)-4-(dibromomethyl)benzene (4)
To a solution of 1,5-dibromo-2,4-dimethylbenzene (1a; 3.25 g, 12.3
mmol) in DCE (120 mL), benzoyl peroxide (63 mg, 0.26 mmol) and
NBS (7.5 g, 42.1 mmol) were added in a single portion. The mixture
was heated to reflux and an additional portion of benzoyl peroxide
(180 mg, 0.74 mmol) was added. The reaction mixture was stirred at
reflux for 2 h and then cooled to room temperature. The precipitated
solid was filtered off and rinsed with hexane (150 mL). The combined
filtrates were concentrated under reduced pressure and purified by
flash column chromatography (petroleum ether) to give 4 as a white
solid (3.17 g, 52% yield); mp 101–102 °C (from hexane).
IR (KBr): 3304, 2938, 2836, 1660, 1444, 1329, 1307, 1208, 1170, 1087,
1056, 985, 904, 777, 683 cm–1
.
1H NMR (200 MHz, CDCl3): δ = 10.07 (s, CHO).
13C NMR (50 MHz, CDCl3): δ = 183.2, 142.1, 123.6.
HRMS (EI): m/z [M]+ calcd for C6H2O2SBr2: 295.81425; found:
IR (KBr): 3452, 3080, 3011, 1581, 1458, 1433, 1365, 1245, 1210, 1149,
295.81346.
1056, 972, 905, 874, 760, 723, 694, 593 cm–1
.
Anal. Calcd for C6H2O2SBr2: C, 24.19; H, 0.68; S, 10.74. Found: C,
24.23; H, 0.72; S, 10.68.
1H NMR (500 MHz, CDCl3): δ = 8.09 (s, 1 H, ArH), 7.76 (s, 1 H, ArH),
6.96 (s, 1 H, CHBr2), 4.57 (s, 2 H, CH2Br).
13C NMR (125 MHz, CDCl3): δ = 140.4, 138.0, 136.5, 133.1, 126.1,
119.9, 38.0, 31.7.
Crystal Structure Data for 1,4-Dibromo-2,5-dimethylbenzene (1b)
C8H8Br2, M = 263.96, monoclinic, space group P21/n (No. 14), a =
6.3264(4) Å, b = 10.6529(6) Å, c = 6.5012(5) Å, β = 97.757(7)°, V =
430.47(5) Å3, Z = 2, T = 290(2) K, Dcalcd = 2.036 g·cm–3, Mo Kα radiation,
2θmax = 50.30°, 8072 reflections collected, 770 reflections unique and
686 reflections with I > 2σ(I). Final GOF = 1.129, R1 = 0.0333 and wR2 =
0.0747 for 686 reflections and 48 parameters.
HRMS (EI): m/z [M]+ calcd for C8H5Br5: 495.63086; found: 495.63126.
Anal. Calcd for C8H5Br5: C, 19.19; H, 0.70. Found: C, 19.23; H, 0.97.
2-Bromo-1,3-bis(dibromomethyl)benzene (2c)
To a solution of 2-bromo-1,3-dimethylbenzene (1c;15 1.00 g, 5.4
mmol) in refluxing DCE (40 mL), Br2 (1.38 mL, 27 mmol) was added
dropwise. The resulting mixture was refluxed under incandescent ir-
radiation (100 W) for 2 h. After cooling to room temperature, the re-
action mixture was quenched with an aqueous solution of NaHSO3.
The organic layer was dried over MgSO4 and evaporated to dryness to
give 2c (2.5 g, 93% yield) as a white solid; mp 151–152 °C (from EtOH)
(Lit.9 150–151 °C).
Crystal Structure Data for 4,6-Dibromo-1,3-benzenedicarbalde-
hyde (3a)
C8H4Br2O2, M = 291.93, monoclinic, space group P21/c (No. 14), a =
3.9947(2) Å, b = 33.386(2) Å, c = 6.3449(5) Å, β = 92.227(5)°, V =
845.56(9) Å3, Z = 4, T = 290(2) K, Dcalcd = 2.293 g·cm–3, Mo Kα radiation,
2θmax = 50.38°, 14951 reflections collected, 1513 reflections unique
and 1311 reflections with I > 2σ(I). Final GOF = 1.209, R1 = 0.0576 and
wR2 = 0.1217 for 1311 reflections and 115 parameters.
IR (KBr): 3024, 1420, 1254, 1149, 1022, 937, 721, 625 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.09 (d, JHH = 7.7 Hz, 2 H, ArH), 7.57 (t,
JHH = 7.9 Hz, 1 H, ArH), 7.18 (s, 2 H, CHBr2).
13C NMR (125 MHz, CDCl3): δ = 140.7, 132.5, 129.1, 39.4.
Crystal Structure Data for 2,5-Dibromo-1,4-benzenedicarbalde-
hyde (3b)
HRMS (EI): m/z [M]+ calcd for C8H5Br5: 495.63087; found: 495.63109.
C8H4Br2O2, M = 291.93, triclinic, space group P1 (No. 2), a = 4.0109(5)
Å, b = 6.2592(9) Å, c = 8.7639(12) Å, α = 72.851(13)°, β = 81.962(11)°,
γ = 85.694(11)°, V = 207.93(5) Å3, Z = 1, T = 290(2) K, Dcalcd = 2.331
g·cm–3, Mo Kα radiation, 2θmax = 50.34°, 2851 reflections collected,
744 reflections unique and 552 reflections with I > 2σ(I). Final GOF =
0.946, R1 = 0.0368 and wR2 = 0.0805 for 552 reflections and 58 param-
eters.
Anal. Calcd for C8H5Br5: C, 19.19; H, 1.01. Found: C, 19.23; H, 0.98.
3,4-Dibromo-2,5-bis(dibromomethyl)thiophene (2d)
A solution of 2,5-dimethylthiophene (1d; 1.00 g, 8.9 mmol) in reflux-
ing DCE (40 mL) was treated dropwise with Br2 (7.11 g, 2.28 mL, 44.5
mmol) over 40 min. The resulting mixture was refluxed under incan-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

F
A. Bodzioch et al.
Paper
Synthesis
Diffraction data were collected using an Oxford Diffraction Xcalibur™
3 diffractometer. The structures were solved by direct methods and
refined by full-matrix least-squares on F2 with SHELX-97.16 The non-
hydrogen atoms were refined anisotropically. All aromatic and meth-
yl (in 1b) H atoms were positioned geometrically and constrained to
ride on their parent atoms, with Uiso(H) values of 1.2 Ueq(Caromatic) and
1.5 Ueq(Cmethyl). The formyl H atoms (in 3a and 3b) were located in dif-
ference maps and refined with Uiso(H) set at 1.2 Ueq(C). CCDC 1454291
(1b), CCDC 1454292 (3a) and CCDC 1454293 (3b) contain the supple-
mentary crystallographic data for this paper. The data can be ob-
tained free of charge from The Cambridge Crystallographic Data Cen-
tre via www.ccdc.cam.ac.uk/getstructures.
Watanabe, S. Tetrahedron 2013, 69, 1904. (d) Buu-Hoi, N. P.;
Nguyen, D.-X.; Nguyen, V.-B. Proc. Int. Conf. Methods Prep. Stor.
Label. Compounds 1968, 215.
(2) Lin, S.-H.; Wu, F.-I.; Liu, R.-S. Chem. Commun. 2009, 45, 6961.
(3) Shen, P.; Sang, G.; Lu, J.; Zhao, B.; Wan, M.; Zou, Y.; Li, Y.; Tan, S.
Macromolecules 2008, 41, 5716.
(4) Shi, Z.; Zhang, X.; Yang, G.; Su, Z.; Cui, Z. Tetrahedron 2011, 67,
4110.
(5) Zhang, X.; Li, M.; Shi, Z.; Zhao, L.; Jin, R.; Yi, M.; Zhang, D.; Cui, Z.
Dyes Pigm. 2012, 92, 982.
(6) Neo, W. T.; Cho, C. M.; Song, J.; Chin, J. M.; Wang, X.; He, C.;
Chan, H. S. O.; Xu, J. Eur. Polym. J. 2013, 49, 2446.
(7) (a) Bałczewski, P.; Skalik, J.; Uznański, P.; Guziejewski, D.;
Ciesielski, W. RSC Adv. 2015, 5, 24700. (b) Bałczewski, P.;
Bodzioch, A.; Skalik, J.; Koprowski, M. EPO Appl. No EP
121877088, 2012.
Acknowledgment
(8) Tietze, L. F.; Krahnert, W.-R. Chem. Eur. J. 2002, 8, 2116.
(9) Harvey, R. G.; Dai, Q.; Ran, C.; Penning, T. M. J. Org. Chem. 2004,
69, 2024.
(10) Zhang, Y.; Song, G.; Ma, G.; Zhao, J.; Pan, C.-L.; Li, X. Organome-
tallics 2009, 28, 3233.
The scientific work was financed from the Science Resources 2008–
2017 as research grants N N204 517139, UMO-2013/11/B/ST5/01610,
2012/05/N/ST5/00169, 2012/07/N/ST5/01985 and from IEP grant
(POIG) No. 10-047/10, Action 1.3.2: ‘Support for the protection of in-
dustrial property formed in scientific units as a result of R+D work’.
(11) Alfonsi, K.; Colberg, J.; Dunn, P. J.; Fevig, T.; Jennings, S.;
Johnson, T. A.; Kleine, H. P.; Knight, C.; Nagy, M. A.; Perry, D. A.;
Stefaniak, M. Green Chem. 2008, 10, 31.
(12) Levine, D. R.; Caruso, A. Jr.; Siegler, M. A.; Tovar, J. D. Chem.
Commun. 2012, 48, 6256.
(13) (a) Amijs, C. H. M.; van Klink, G. P. M.; van Koten, G. Green. Chem.
2003, 5, 470. (b) Mestres, R.; Palenzuela, J. Green Chem. 2002, 4,
314. (c) Offermann, W.; Vögtle, F. Synthesis 1977, 272.
(14) Liu, Z.; Yasseri, A. A.; Loewe, R. S.; Lysenko, A. B.; Malinovskii, V.
L.; Zhao, Q.; Surthi, S.; Li, Q.; Misra, V.; Lindsey, J. S.; Bocian, D. F.
J. Org. Chem. 2004, 69, 5568.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561651.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F