2-Bromo-5-iodo-hydroquinone and its symmetrical and unsymmetrical dialkylethers

Article abstract of DOI:10.1515/znb-1998-0905

2-Bromo-5-iodo-hydroquinone dialkylethers are prepared by the stepwise halogenation and alkylation of hydroquinone monoalkylethers using simple and easily performable reactions. Boron tribromide induced cleavage of the dipropoyl ether gives the parent com

Full text of DOI:10.1515/znb-1998-0905

2-Bromo-5-iodo-hydroquinone and its Symmetrical and Unsymmetrical
Dialkylethers
Sigurd Höger*, Klaus Bonrad, Gabriele Schäfer, Volker Enkelmann
Max-Planck-Institut für Polymerforschung, Ackermannweg 10, D-55128 Mainz, Germany
Z. Naturforsch. 53 b, 960-964 (1998); received May 29, 1998
Hydroquinones, Building Blocks for Nanostructures, Halogenation, Ipso Substitution
2-Bromo-5-iodo-hydroquinone dialkylethers are prepared by the stepwise halogenation and
alkylation of hydroquinone monoalkylethers using simple and easily performable reactions.
Boron tribromide induced cleavage of the dipropoyl ether gives the parent compound 2-bromo-
5-iodo-hydroquinone in good yields.
Synthetic methods for the formation of well de- the preparation of the intermediate trimethylsilyl
compound and introduction of the iodo function by
region have attracted considerable interest over the ipso iododesilylation [7]. However, in general these
methodologies do not allow for the regioselective
ration of dendritic macromolecules as well as con- lithiation, so that only symmetrical alkylated aro-
fined and monodisperse objects in the nanometer
last few years. Several strategies allow for the prepa-
matic systems can be prepared in a defined matter.
Here we describe the synthesis of 2-bromo-5-
iodo-hydroquinone (1 ), and one example of both its
symmetrical and unsymmetrical dialkylethers (2a
and 2b). The latter substitution pattern is not avail-
able by the protocol described above, and therefore
our attempt focused on the stepwise halogenation
and alkylation of hydroquinone monoalkylethers.
The synthesis described here is based on the fol-
lowing two findings. First, bromination of acylated
hydroquinone monoalkyl ethers occurs selectively
at the position ortho to the phenol ether position [8],
and second, halogenation of bromo-hydroquinone
dialkyl ethers occurs in para position to the first
bromide.
4-Propyloxyphenol (3) was acylated using stan-
dard conditions to give 4, which was brominated
selectively at the position ortho to the phenol ether
substituent. Even with an excess of bromine only
clean mono substitution was observed under the
conditions we used. After base catalysed depro-
tection of 5, 6 was alkylated to give 7a and 7b,
respectively. Iodination using F/HIO3 afforded the
symmetrical (2a) and unsymmetrical (2b) 2-bromo-
5-iodo-hydroquinone dialkylethers. In this connec-
tion it is interesting to note that the bromination of
l-iodo-2,5-dipropyloxy-benzene [9] with 1.5 equiv-
alents of bromine in CH2CI2 at 0 °C gives ex-
clusively 1,4-dibromo-2,5-dipropyloxy-benzene in
nearly quantitative yield. This unexpected result can
trolled oligomers, most of them use repetitive strate-
gies [1]. In order to avoid the use of a large excess
of one coupling component, it is common to use un-
symmetrical building blocks of the AB-type. In this
case A and B show either orthogonal reactivities [2]
or one of these groups is a protective group which
has to be transformed into a reactive group prior
to the subsequent step [3]. An alternative strategy
makes use of different reactivities of the groups A
and B (dormant group strategy) in which case A
and B can, in principle, be transformed in a one-
pot reaction [4]. Since the reactivity of aryl halo-
gen bonds towards the insertion of palladium(O)
species decreases in the order Arl > ArBr, aromatic
compounds containing both bromide and iodide are
useful building blocks for the construction of nanos-
tructures using repetitive strategies [5, 6 ]. The prob-
lem of low solubility of the target molecules can be
avoided by attaching alkyl- or alkoxy side chains
to the aromatic nucleus. Nevertheless, only few ex-
amples of aromatic compounds containing bromide
and iodide in the 1,4-position as well as solubilis-
ing side chains are reported in the literature. They
are mostly prepared by monolithiation of the cor-
responding dibromide, and quenching of the an-
ion with diiodoethane. An alternative procedure is
* Reprint requests to Dr. S. Höger;
Fax: +49 6131 379 100.
K
0932-0776/98/0900-0960 $ 06.00 © 1998 Verlag der Zeitschrift für Naturforschung, Tübingen • www.znaturforsch.com
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S. Höger et al. • 2-Bromo-5-iodo-hydroquinone and its Symmetrical and Unsymmetrical Dialkylethers
961
OAc
Br?
k 2c o 3
RX
quant.
9 5 %
OC3H7
4
K - Ac
‘•pyndine
92%
BBr3
i2/h io 3
o c 3h 7
o c 3h 7
Scheme 1. Synthesis of the title
compounds.
2 a (91 %) R = C3H7
2 b (71 %) R = C 12H25
7 a (94 %) R = C3H7
7 b (48% ) R = C 12H25
(86 % from 2a)
be explained by the larger tendency of iodide to un- (40.0 g, 0.26 mol) and pyridine (30.9 g, 0.39 mol) in THF
(20 ml). The mixture was stirred for 12 h and poured into
Et20 (600 ml) and water (500 ml). The organic phase
was extracted with 10 % aqueous HOAc (4 x 200 ml),
water (200 ml), 10 % aqueous NaOH (2 x 200 ml), and
brine (200 ml), and dried (MgSÜ4). After evaporation of
the solvent, the oil was purified by distillation (b. p.: 73
- 75 °C, 10_l mbar) to yield 46.6 g (92 %) of 4 as a
colourless oil. - 'H NMR: 6 = 1.00 (m, 2 H), 6.90 (m,
2 H), 3.92 (t, 7 = 6.7 Hz, 2 H), 2.62 (s, 3 H), 1.82 (m, 2 H),
1.05 (t, 7 = 7.5 Hz, 3 H). - 13C NMR: 8 = 170.52, 157.71,
144.98, 115.69, 70.72, 23.39, 21.56, 11.04.-M S: m/z =
193.9(87) [M+], 151.9 (100) - [M+-C3H6], 109.8(49).
dergo ipso substitution [10].
Cleavage of the ether bonds of 2a with BBr3 gave
the parent compound 1. 1, and the symmetrically
substituted 2,5-dibromo-hydroquinone [11] crystal-
lize in isomorphous crystal structures exhibiting hy-
drogen bonded sheets (Fig. 1) [12]. The structure of
1 is disordered, the iodo and the bromo atoms sta-
tistically occupy identical positions.
All transformations described above are easy to
perform. None of the reactions for the preparation
of 2 requires oxygen or moisture sensitive reagents.
In most cases, they give high to nearly quantita-
tive yields and therefore allow for the preparation
of bromo-iodo-hydroquinone dialkyl ethers in large
quantities. The parent compound 1 is described here
for the first time.
Analysis for C11H14O3
Calcd C 68.02 H 7.27 %,
Found C 67.84 H 7.33 %.
Acetic acid-(3-bromo-4-propyloxyphenyl)-ester (5)
To a stirred suspension of acetic acid-(4-propyloxy-
phenyl)-ester (4) (50.5 g, 0.26 mol) and NaOAc (18.9 g,
0.23 mol) in HOAc (100 ml) was added dropwise bromine
(62.4 g, 0.39 mol) at room temperature. The solution was
stirred overnight and poured into Et2 0 (500 ml). The
organic phase was extracted with water (250 ml), 10 %
aqueous NaOH (4 x 150 ml), concentrated Na2S2 0 3-
solution(2 x 100 ml), water (150 ml), brine (200 ml), and
dried (MgS0 4 ). The solvent was removed. The residue
was distilled (b. p.: 108 °C, 10_l mbar) to yield 67.5 g
(95%) of 5 as a colourless oil. - 1H NMR: 6 = 7.30 (d, 7 =
2.7 Hz, 1H), 7.01 (dd, V = 8.8 Hz, 4J = 2.7 Hz, 1H), 6.89
(d, 7 = 9.1 Hz, 1H), 3.98 (t, 7= 6.3 Hz, 2 H), 2.25 (s,3H),
1.84 (m, 2 H), 1.07 (t, 7 = 7.3 Hz, 3 H). - 13C NMR: 6 =
169.45, 153.66, 144.23, 126.53, 121.58, 113.24, 111.86,
Experimental Section
Commercially available chemicals were used as re-
ceived. 'H NMR and l3C NMR spectra were recorded in
CD2CI2 on a Bruker AC300 (300 MHz for proton and
75.48 MHz for carbon) and chemical shifts are given
relative to TMS or solvent signals. Mass spectra were
obtained by electron impact (El) on a Trio 2000 (VG In-
struments). TLC was performed on Merck silica gel 60
F254 plates. Column chromatography was run on Merck
Kieselgel 60 (230-400 mesh).
Acetic acid-(4-propyloxyphenyl)-ester (4)
AC2O (40.6 g , 0.39 mol) was slowly added at room
temperature to a stirred solution of 4-propyloxyphenol (3)
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962
S. Höger et al. • 2-Bromo-5-iodo-hydroquinone and its Symmetrical and Unsymmetrical Dialkylethers
Fig 1. X-ray structure of 1. 0- • 0 distance within the sheets: 2.778 Ä (Z 0 -0 -0 120.8°). oaxis is horizontal aligned,
b-axis is vertical aligned.
90 °C, 10“ 1mbar). - 1H NMR: 6 = 7.12 (m, 1H), 6.82 (m,
2 H ),3.91 (t,7 = 6.5 Hz, 2 H), 3.85 (t, 7 = 6.5 Hz,2H), 1.75
- 1.83 (m, 4 H), 1.06 (t, J = 6.5 Hz, 3 H), 1.02 (t, J = 6.5
Hz, 3 H ).- ,3C NMR: b = 154.41,150.54,120.26,115.42,
115.14, 113.25,72.37.71.14, 23.47, 23.38, 11.12, 11.01.
- MS : m/z = 271.9 (96) [M+], 229.8 (8) [M+-C3H6], 187.7
(29) [M+- 2 (C3H6)].
71.35,22.61, 20.88, 10.96. - MS : m/z = 272.0 (28) [M+],
230.0 (54) [M+-C3H6], 188 (49), 51 (100).
Analysis for CnHnBrO^
Calcd C 48.37 H4.80%,
Found C 48.48 H4.59%.
3-Bromo-4-propyloxyphenol (6)
The saturated aqueous solution of K2CO3 (72.0 g, 0.52
mol) was slowly added to a suspension of acetic acid-(3-
bromo-4-propyloxy)-phenylester (5) (70.0 g, 0.26 mol)
in MeOH (45 ml)/H2 0 (25 ml). After stirring overnight
the mixture was acidified with 10 % aqueous HC1, and
the resulting suspension was extracted with Et20 (3 x
200 ml). The combined Et2 0 layers were washed with
water ( 2 x 1 0 0 ml), brine ( 2 0 0 ml), and dried (MgS0 4 ).
The solvent was evaporated to yield 6 quantitatively as a
brown oil. - 1H NMR: 6 = 7.07 (d, J = 3.0 Hz, 1 H), 6.81
(d, J = 8 .8 Hz, 1 H), 6.75 (dd, 3J = 8 .8 Hz, V = 2.7 Hz,
1 H), 5.21 (br s, 1 H), 3.91 (t, J = 6.5 Hz, 2 H), 1.80 (m,
2 H), 1.05 (t, J = 7.5 Hz, 3 H). - l3C NMR: 6 = 150.2,
120.3, 115.2, 112.7,71.9, 22.7, 10.4.-M S : m/z = 229.8
(100) [M+], 187.8 (6 6 ) [M+-C3H6], 141.9 (39).
Analysis for Ci2HnBr02
Calcd C 52.76 H 6.27 %,
Found C 52.50 H 6.27 %.
1-Bromo-5-dodecanyloxy-2-propyloxy-benzene (7b)
The mixture of 2-bromo-4-propyloxyphenol (6),
(4.62 g, 20 mmol), 1-bromododecane (6.23 g, 25 mmol)
and K2CO3 (4.15 g, 30 mmol) in acetone (40 ml) was re-
fluxed for 12 h. After cooling down at room temperature
the suspension was filtered and the solvent was evapo-
rated. The residue was purified by column chromatogra-
phy (petrolether/CH2Cl2 70:9, Rf = 0.42) to yield 3.84
g (48 %) of pure 7b as an oil. 'H NMR: 6 = 7.11 (d, J
= 2.7 Hz, 1 H), 6.84 (d, J = 8.8 Hz, 1 H), 6.79 (dd, V
= 8.8 Hz, V = 2.7 Hz, 1 H), 3.91 (t, J = 6.5 Hz, 2 H),
3.88 (t, J = 6.5 Hz, 2 H), 1.75 (m, 4 H), 1.28 (m, 18 H),
1.06 (t, J = 7.3 Hz, 3 H), 0.89 (t, J = 6.9 Hz, 3 H). -
13C NMR: 6 = 153.86, 149.94, 119.65, 114.83, 114.53,
112.69, 71.78, 68.05, 32.13, 29.87, 29.84, 29.80, 29.78,
29.57, 29.56, 29.46, 26.17, 22.88, 14.07, 10.50. - MS:
m/z = 398.2 (40) [M+], 356.1 (8) [M+-C3H6], 230.0 (10)
[M+-C12H24], 188 (100) [M+-C3H6, -C12H24], 109.8 (10)
[M+-C3H6, -C12H24 , -Br], 85.3 (18), 69.3 (30), 57.5 (55).
Analysis for C9 H11 Br0 2
Calcd C 46.78 H4.80%,
Found C 46.62 H4.81 %.
l-Bromo-2,5-dipropyloxy-benzene (7a)
The mixture of 3-bromo-4-propyloxyphenol (6 ), (49.0
g, 0.21 mol), 1-iodopropane (45.9 g, 0.27 mol) and
(44.2 g, 0.32 mol) K2CO3 in acetone (400 ml) was re-
fluxed for 12 h. The hot suspension was filtered after
which the solvent was evaporated. Distillation of the
residue gave 53.9 g (94 %) of 7a as a yellow oil (b. p.:
Analysis for C21 H3_<;Br02
Calcd C 63.15 H 8.83 %,
Found C 63.17 H 8.84 %.
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S. Höger et al. • 2-Bromo-5-iodo-hydroquinone and its Symmetrical and Unsymmetrical Dialkylethers_________963
1-Bromo-4-iodo-2,5-dipropyloxy-benzene (2a)
6 = 152.74, 150.53, 124.41,117.19, 112.51,84.78,71.97,
70.50, 32.04, 29.77, 29.75, 29.69, 29.67, 29.46, 29.38,
29.24, 26.12, 22.80, 22.70, 13.98, 10.35. - MS: m/z =
524.0 (43) [M+], 481.9 (3) [M+-C3H6], 439.7 (6 ), 355.9
(31) [M+-C12H24], 313.8 (90) [M+-C3H6, -C12H24], 234.4
(3) [M+ -C3H6, -C12H24, -Br], 187.6 (10), 83.3 (18), 69.3
(55), 55.6(100).
A mixture of 1-Bromo-2,5-dipropyloxy-benzene (7a)
(27.3 g, 100 mmol), iodine (25.3 g, 100 mmol) and iodic
acid (8.80 g, 50 mmol) in CCI4 (16 ml), 30 % aque-
ous H2SO4 ( 1 2 ml), and acetic acid (64 ml) was stirred
for 12 h at 75 °C. After cooling down at room temper-
ature, Et2Ü (500 ml), water (300 ml) and concentrated
Na2S2C>3-solution (100 ml), were carefully added. The
organic phase was extracted with concentrated Na2S2 0 }-
solution (2 x 75 ml), 10 % aqueous NaOH (2 x 200 ml),
water (2 x 200 ml), brine (200 ml), and dried (MgSOa).
The solvent was removed and the residue was recrystal-
lized from CHCI3 (30ml) to give 36.3 g (91 %) of 2a as
yellow needles (m.p.: 70 - 72 °C). - 'H NMR: 6 = 7.31
(s, 1 H), 7.01 (s, 1 H), 3.91 (t, J = 6.5 Hz, 2 H), 3.90
(t, J = 6.5 Hz, 2 H), 1.74 - 1.87 (m, 4 H), 1.07 (t, J =
7.5 Hz, 3 H), 1.05 (t, J = 7.5 Hz, 3 H), l3C NMR: 6
= 153.35, 151.20, 125.04, 113.17, 117.84, 85.47, 72.62,
23.39, 11.25, 11.07. - MS: m/z = 398.0 (41) [M+], 356.9
(21) [M+-C3H6], 313.8 (100) [M+- 2 (C3H6)]
Analysis for C2iH34BrI02
Calcd C 48.02 H 6.52 %,
Found C 47.91 H 6.46 %.
2-Bromo-5-iodo-hydroquinone (1)
A solution of l-bromo-4-iodo-2,5-dipropyloxy-ben-
zene (2a) (2.00 g, 5 mmol) in CH2CI2 (20 ml) was cooled
down at -78 °C. During 15 minutes borontribromide(3.76
g, 15 mmol) in CH2CI2 (10 ml) was dropewise added. The
cooling bath was taken away and the mixture was stirred
overnight. After adding water (20 ml) cautiously, the so-
lution was poured into ether (400 ml) and water (200 ml).
The organic phase was extracted with water (2 x 200
ml), brine (200 ml) and dried (MgS0 4 ). The solvent was
evaporated to yield 1.35 g (86 %) of 7 as a colourless
powder (m.p.: 186 °C). - 1H NMR (DMSO): 6 = 9.89 (br
s, 1 H), 9.74 (br s, 1 H), 7.22 (s, 1 H), 6.95 (s, 1 H). -
,3C NMR (DMSO): 6 = 150.25, 147.79, 125.28, 118.18,
109.42, 83.14. - MS (El): m/z = 314.0 [M+] (100), 187.0
(15) [M+ -I],159 (11), 127.0 (20) [I], 107.0 (30) [M+ -I,
-Br], 79.0 (32).
Analysis for Ci2Hi6 BrI0 2
CalcdC 36.12 H 4.04%,
Found C 35.97 H 4.09%.
l-Bromo-5-dodecanyloxy-4-iodo-2-prop\loxy-benzene
(2b)
The iodination of l-Bromo-5-dodecanyloxy-2-propyl-
oxy-benzene (7b) was performed under the same con-
ditions like the analogous reaction from l-Bromo-2,5-
dipropyloxy-benzene (7a). The residue was purified by
column chromatography (petrolether/CH2Cl2 70:9, Rf =
0.60) to yield 1.87 g (71 %) of 2b as a colourless pow-
der (m.p.: = 4 1 -4 2 °C). - 'H NMR: 6 = 7.31 (s, 1 H).
7.01 (s, 1 H), 3.91 (t, J = 6.7 Hz, 2 H), 3.90 (t, J = 6 .6
Hz, 2 H), 1.80 (m, 4 H), 1.25 - 1.41 (m, 18 H), 1.05 (t, J
= 7.4 Hz, 3 H), 0.88 (t, J = 6.7 Hz, 3 H), ,3C NMR:
Analysis for C6H4BrI02
Calcd C 22.88 H l.28% ,
Found C 23.02 H 1.29%.
Acknowledgement
A part of this work was supported by the Volkswagen-
stiftung.
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S. Höger et al. • 2-Bromo-5-iodo-hydroquinone and its Symmetrical and Unsymmetrical Dialkylethers
964
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a = 6. 302(1), b = 4. 832(1), c = 13. 411(1) Ä; ß
= 102. 639(5)°, Z = 2, Dx = 2. 626 gem-3. Least
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mationszentrum Karlsruhe, Gesellschaft für wissen-
schaftlich-technische Information mbH, D-76344
Eggenstein-Leopoldshafen, on quoting the deposi-
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alkylation of 3-iodo-4-propyloxyphenol4a using 1-
bromopropane/KaCO? in DMF at 70 °C.
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