Efficient synthesis of octaalkyloxy-o-quaterphenyls via base-induced biaryl coupling

Article abstract of DOI:10.1055/s-1999-3412

Octamethoxy-o-quaterphenyl (8a) was prepared in three steps from 4- bromo-1,2-dimethoxybenzene (5a) employing two base-mediated biaryl couplings. Demethylation of 8a followed by alkylation with decyl bromide gave the tetradecyloxy-o-quaterphenyl (8c).

Full text of DOI:10.1055/s-1999-3412

PAPER
475
Efficient Synthesis of Octaalkyloxy-o-quaterphenyls via Base-Induced
Biaryl Coupling
Jšrg L. Schulte, Sabine Laschat*
Institut fŸr Organische Chemie der Technischen UniversitŠt Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany
Fax +49(531)3915388; E-mail: S.Laschat@tu-bs.de
Received 14 August 1998
Abstract: Octamethoxy-o-quaterphenyl (8a) was prepared in three
steps from 4-bromo-1,2-dimethoxybenzene (5a) employing two
base-mediated biaryl couplings. Demethylation of 8a followed by
alkylation with decyl bromide gave the tetradecyloxy-o-quater-
phenyl (8c).
Key words: biaryl coupling, o-quaterphenyl, alkyllithiums
Interest in o-quaterphenyls 1 has been stimulated by dif-
ferent research areas (Scheme 1). Všgtle for example used
bridged, helical o-quaterphenyls (quaterphenylophanes)
to study the dependence of the UV absorption from the
1
twisting of the aryl rings. o-Quaterphenyls were also em-
ployed in host-guest chemistry. The binding properties of
EDTA analogues bearing an o-quaterphenyl central unit
2
towards metal ions were determined by Všgtle. Cram
studied transacylase mimics based upon the quaterphenyl
3
system. It was also found that o-quaterphenyl derivatives
are involved in carbonÐcarbon bond activation processes
catalyzed by Ni, Pd and Pt complexes.
4
,5
Scheme 1
The synthesis of these quaterphenyls relies mainly on the
1
,6
classical Ullmann reaction. In addition Pd-catalyzed (5c) gave the corresponding biphenyls 6b in 37% and 6c
7
Suzuki coupling of aryl boronates, Ni-catalyzed Kumada in 19% yield, respectively (Scheme 2). Although com-
8
coupling of aryl Grignard reagents, Cu(II)-catalyzed re- pounds 6b,c were obtained in lower yields as compared to
5
a
arrangements of bora-aromatics, oxidative coupling of 6a, the tetradecyloxy derivative 6b in particular is worth
9
metal phenolates, and oxidative addition of Ni(0) com- mentioning, because it is an important precursor for the
plexes to biphenylene were used as well.4b We have re- synthesis of discotic liquid crystals bearing the tri-
1
4,15
cently found that 3,3',4,4'-tetramethoxybiphenyl 6a (R = phenylene moiety.
Me) could be prepared in 79% yield by treatment of 4-bro-
mo-1,2-dimethoxybenzene 5a with 0.5 equivalents of bu-
tyllithium in THF at Ð78¡C (Scheme 2).10,11 The formation
of 6a had been observed previously during bromine-lithi-
1
2d
um exchange in 5a with butyllithum. We anticipated
that this clean biaryl formation, which does not require the
1
2
use of expensive or toxic coupling agents might be use-
ful for the synthesis of o-quaterphenyl derivatives 1 as
outlined in Scheme 1. We were particularly interested in
o-quaterphenyls 1 with long alkyl or alkoxy chains as po-
tential new liquid crystals. The results towards this end are
reported below.
A preliminary study revealed the scope and limitations of
the base-induced biaryl coupling. Whereas most aryl
bromides, like 4-bromobenzene, 1-bromonaphthaline,
4
4
-bromo-N,N'-dimethylaniline, 1-bromo-4-nitrobenzene,
-bromoanisole, and 1-bromo-2,4-dimethoxybenzene ei-
ther did not react in the presence of 0.5 equivalents of bu-
1
3
tyllithium in THF or gave the butylated products, only
-bromo-1,2-didecyloxybenzene 5b and 2-bromoanisole
Scheme 2
4
Synthesis 1999, No. 3, 475Ð478 ISSN 0039-7881 © Thieme Stuttgart á New York

4
76
J. L. Schulte, S. Laschat
PAPER
Due to the tedious chromatographic separations of de- the quaterphenyl are equivalent. A similar behaviour was
cyloxy substituted compounds we decided to carry the observed for 8a,c. Differential scanning calorimetry of
methoxy groups through the synthesis in order to replace 8aÐc revealed no liquid crystalline properties. All
it by decyl substituents in the final steps. Thus 3,3',4,4'- o-quaterphenyl derivatives 8aÐc showed isotropic melting.
tetramethoxybiphenyl (6a) was brominated to give 7 in
In conclusion, the base-induced aryl coupling is limited to
6
7
0% yield (Scheme 3). Base-induced coupling of bromide
to the o-quaterphenyl 8a proceeded cleanly in the pre-
3
,4-dialkoxyaryl bromides 5a,b. However it can be used
both for the synthesis of biphenyls 6aÐc and the novel
quaterphenyl 8a.
sence of tert-butyllithium in 55% yield. In this case butyl-
lithium was not sufficient. The smooth coupling towards
8
a is remarkable regarding the increased steric hindrance
All reactions were carried out under N using standard Schlenk
of 7 as compared to 5a. After demethylation of 8a with
2
boron tribromide14 the octahydroxy-o-quaterphenyl 8b
techniques. Solvents were dried and deoxygenated by standard pro-
cedures. Analytical TLC was performed on precoated Merck Si 254
F plates (0.25 mm thickness) and the products were visualized by
spraying with a solution of phosphomolybdic acid in EtOH (5%, v/
was obtained in 45% yield. Subsequent alkylation of 8b
with decyl bromide gave the quaterphenyl 8c in 64%
yield.
16
v). Flash chromatography was carried out with Merck silica gel 60
1
(
5
230 Ð 400 mesh). NMR spectra: Bruker AC 200 P (200 MHz H,
0 MHz 13C). Multiplets in C NMR spectra were assigned with the
13
aid of DEPT experiments. Melting points were determined by dif-
ferential scanning calorimetry with a Rheometric Scientific DSC
Ð1
SP, heating and cooling rate: 10 K min . IR: Nicolet 5DXC FT-IR
spectrometer. MS: Finnigan Model MAT 8430 (EI). 4-Bromo-1,2-
dimethoxybenzene 5a and 2-bromoanisole (5c) were purchased
from Aldrich. 1,2-Didecyloxybenzene was prepared according to
the literature procedure.1
5a
3
,3',4,4'-Tetradecyloxybiphenyl (6b)
To an ice-cooled solution of 1,2-didecyloxybenzene (39.1 g,
.10 mol) in CHCl (250 mL) was added Br (116 g, 0.72 mol) in
0
3
2
CHCl (70 mL) over 2 h. After stirring was continued for 12 h, the
3
mixture was poured into 10% aq NaHSO solution. The layers were
3
separated and the organic layer was washed with 2 N NaOH
(
100 mL), H O (100 mL), dried (MgSO ) and evaporated to give
2
4
4
2.3 g (90%) of 4-bromo-1,2-didecyloxybenzene (5b) as a colorless
amorphous solid. To a solution of 5b (40.5 g, 86.2 mmol) in THF
250 mL) was added dropwise BuLi (26.9 mL, 43.1 mmol, 1.6 M
(
solution in hexane) over 30 min at Ð13¡C and the resulting mixture
was warmed to r.t. over 19 h. After hydrolysis with 2 N HCl
(50 mL), the layers were separated and the aqueous layer was ex-
tracted with CH Cl (3 × 100 mL). The combined organic layers
2
2
were dried (MgSO ) and evaporated to yield a pale yellow solid,
4
which was twice recrystallized from EtOH (250 mL) and hexane
(125 mL), respectively, to give 12.3 g (37%) of a colorless, amor-
phous solid. The analytic and spectroscopic data are in accordance
with References 17 and 18.
2
,2'-Dimethoxybiphenyl (6c)
Following the procedure described for 6b, a solution of o-bro-
moanisole (9.35 g, 50.0 mmol) in THF (100 mL) was treated with
BuLi (15.6 mL, 25.0 mmol, 1.6 M solution in hexane) at Ð78¡C to
give after hydrolysis, workup, flash chromatography on silica gel
(hexanes/EtOAc, 20:1) and recrystallization from EtOH (50 mL)
1
.01 g (19%) of a colorless solid; mp 155¡C. The analytical, IR and
MS data are in accordance with References 19 and 20.
1
H NMR (200 MHz, CDCl ): d = 7.36Ð7.22 (m, 4 H), 7.03Ð6.93 (m,
3
4
H), 3.74 (s, 6 H, OCH3).
13C NMR (50 MHz, CDCl
28.6 (C-4/C-4'), 127.8 (C-1/C-1'), 120.3 (C-5/C-5'), 111.1
Scheme 3
3
): d = 157.0 (C-2/C-2'), 131.5 (C-6/C-6'),
1
1
13
(C-3/C-3'), 55.7 (OCH3).
According to the H and C NMR spectra a C -symmet-
2
ric, propeller-shaped conformation can be assigned for the
1
3
2-Bromo-4,4',5,5'-tetramethoxybiphenyl (7)
target compounds 8aÐc. For example the C NMR spec-
trum of quaterphenyl 8b shows only four quaternary CÐ
OH signals, three quaternary Caryl signals and five tertiary
To an ice-cooled solution of biphenyl 6a (35.0 g, 0.13 mol) in
CHCl (75 mL) was added dropwise a solution of Br (20.5 g,
3
2
0.13 mol) in CHCl (250 mL) over 3 h and stirring was continued
3
CHaryl signals, indicating that the two biphenyl moieties of for 1 h. Then the mixture was washed with aq satd NaHSO solution
3
Synthesis 1999, No. 3, 475Ð478 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Efficient Synthesis of Octaalkyloxy-o-quaterphenyls via Base-Induced Biaryl Coupling
477
(
250 mL), 2 N NaOH (250 mL) and H O (250 mL), dried (MgSO ),
2.0 Hz, 2 H, 2-H, 2"'-H), 4.81 (dd, J = 8.2, 2.0 Hz, 2 H, 6-H, 6"'-H),
2
4
and evaporated to yield a solid, which was recrystallized from
EtOH to give 26.9 g (60%) of pale yellow crystals; mp 82¡C.
3.72 (br s, 8 H, 8 × OH).
13
C NMR (50 MHz, CD OD): d = 145.1, 144.9, 144.6, 144.1 (4×
3
IR (KBr): n = 3084, 2993, 2960, 2942, 2906, 2873, 2858, 2854,
COMe), 135.3, 134.5, 133.3 (C-1/C-1"', C-1'/C-2", C-2'/C-1"),
122.2, 119.8, 117.9, 117.6, 115.4 (5×CHaryl).
2
1
1
836, 1598, 1498, 1465, 1452, 1437, 1418, 1370, 1311, 1269, 1246,
207, 1189, 1176, 1144, 1024, 856, 827, 819, 784, 763 cm .
Ð1
MS (EI): m/z = 434 (M, 100), 397 (4), 388 (5), 369 (7), 324 (7), 295
(5), 289 (5), 242 (6), 229 (4), 162 (4), 137 (3), 120 (3), 55 (2).
H NMR (200 MHz, CDCl ): d = 7.11Ð6.85 (m, 5 H, 2'-H, 3-H,
3
3
'-H, 6-H, 6'-H), 3.91Ð3.86 (m, 12 H, OCH3).
Anal. calcd. for C H O : C, 66.36; H, 4.18. Found: C, 66.28; H,
24
18
8
1
3
C NMR (50 MHz, CDCl ): d = 148.6, 148.4, 148.2, 148.2 (C-4,
4.28.
3
C-4', C-5, C-5'), 134.5, 133.8 (C-1, C-1'), 121.7, 115.8, 114.0,
1
5
13.1, 112.6, 110.7 (C-2, C-2', C-3, C-3', C-6, C-6'), 56.2, 56.1,
5.9, 55.8 (OCH3).
3,3''',4,4',4'',4''',5',5''-Octadecyloxy-1,1',2',1'',2'',1'''-quater-
phenyl (8c)
To a suspension of K CO (5.10 g, 36.8 mmol) in DMF (50 mL)
MS (EI): m/z (%) = 354 (M, 100), 352 (99), 339 (25), 337 (25), 311
2
3
were added quaterphenyl 8b (1.00 g, 2.30 mmol) and decyl bromide
4.07 g, 18.4 mmol) and the mixture was heated for 17 h at 120¡C.
(12), 309 (14), 274 (16), 231 (11), 230 (40), 215 (34), 213 (10), 141
8), 126 (8), 115 (12), 113 (8), 75 (6), 63 (6), 45 (16).
(
(
After cooling to r.t., the mixture was poured on ice (100 g) and the
precipitate was isolated by filtration. The crude product was puri-
fied by flash chromatography on silica gel (hexanes/EtOAc, 20:1)
and recrystallization from EtOH (50 mL) to give 2.30 g (64%) of a
colorless powder; mp 33¡C.
Anal. calcd. for C H BrO : C, 54.44; H, 4.85. Found: C, 54.45; H,
1
6
17
4
5
.05.
3
,3''',4,4',4'',4''',5',5''-Octamethoxy-1,1',2',1'',2'',1'''-quater-
phenyl (8a)
IR (KBr): n = 2957, 2924, 2853, 1506, 1469, 1380, 1248, 1198,
To a solution of 7 (31.0 g, 87.8 mmol) in THF (300 mL) was added
dropwise t-BuLi (27.4 ml, 43.9 mmol, 1.6 M solution in hexane)
over 30 min at Ð78¡C. The resulting mixture was allowed to warm
to r.t. over 20 h. Then 2 N HCl (100 mL) was added and the layers
were separated. The aqueous layer was extracted with CH Cl (3 ×
Ð1
1
139, 1071 cm .
1
H NMR (200 MHz, CDCl ): d = 6.84 (s, 2 H, 6'-H, 3"-H), 6.71 (s,
3
2 H, 3'-H, 6"-H), 6.55 (d, J = 8.1 Hz, 2 H, 5-H, 5"'-H), 6.25 Ð 6.20
(m, 4 H, 6-H, 6"'-H, 2-H, 2"'-H), 3.99Ð3.88 (m, 12 H), 3.67Ð3.45
2
2
1
00 mL) and the combined organic layers were dried (MgSO ) and
(m, 4 H) (4 × OCH ), 1.78Ð1.25 (m, 128 H), 0.88 (t, J = 6.4 Hz, 24
4
2
evaporated to yield a yellow solid. After purification by flash chro-
matography on silica gel (hexanes/CH Cl , 1:4, then EtOAc/
H, CH CH ).
2
3
2
2
13
C NMR (50 MHz, CDCl ): d = 148.2, 147.9, 147.8, 147.1
3
CH Cl , 1:9) 13.2 g (55%) of a pale yellow solid was obtained; mp
2
2
(4 × COMe), 134.2, 133.7, 132.4 (C-1/C-1"', C-1'/C-2", C-2'/C-1"),
2
19¡C.
1
21.3, 117.4, 115.5, 115.0, 113.4 (5 x CHaryl), 69.4, 69.4, 68.5
IR (KBr): n = 3083, 2992, 2956, 2935, 2913, 2864, 2835, 1617,
(4 × OCH ), 31.9, 29.7, 29.6, 29.5, 29.4, 29.3, 26.1, 22.7 (CH ),
14.1 (CH3).
3
2
1
1
1
517, 1466, 1451, 1444, 1405, 1261, 1255, 1222, 1205, 1174, 1159,
Ð1
147, 1136, 1074, 1051, 1023, 842, 781 cm .
MS (MALDI-TOF): m/z = 1556 (M).
H NMR (200 MHz, CDCl ): d = 6.95 (s, 2 H, 6'-H, 3"-H), 6.73 (s,
3
Anal. calcd. for C104H178O : C, 80.25; H, 11.52. Found: C, 80.38; H,
8
2
H, 3'-H, 6"-H), 6.57 (d, J = 8.2 Hz, 2 H, 5-H, 5"'-H), 6.21 (dd, J =
.2/2.0 Hz, 2 H, 6-H, 6"'-H), 6.17 (d, J = 2.0 Hz, 2 H, 2-H, 2"'-H),
.90 (s, 6 H), 3.89 (s, 6 H), 3.84 (s, 6 H), 3.53 (s, 6 H) (8 × OCH3).
1
1.49.
8
3
1
3
Acknowledgement
C NMR (50 MHz, CDCl ): d = 148.1, 147.9, 147.8, 147.1
3
(
4 × COMe), 133.7, 133.5, 132.1 (C-1/C-1"', C-1'/C-2", C-2'/C-1"),
Generous Þnancial support by the Deutsche Forschungsgemein-
schaft (Gerhard-Hess-Preis for S.L.) and the Fonds der Chemi-
schen Industrie is gratefully acknowledged. J. L. S. wishes to thank
Ulrich Blaschke for stimulating discussions. We thank Dr. Manfred
Nimtz, Gesellschaft fŸr Biotechnologische Forschung, Braun-
schweig for MALDI-TOF spectra.
1
21.2, 114.6, 112.8, 112.4, 110.4 (5 × CHaryl), 56.1, 56.0, 55.8, 55.4
(4 × OCH3).
MS (EI): m/z (%) = 546 (M, 100), 500 (4), 468 (8), 408 (3), 365 (2),
04 (2), 149 (5), 113 (2), 71 (2), 57 (3).
2
HRMS (EI): m/z calcd. for C H O 546.2253, found 546.2250.
3
2
34
8
Anal. calcd. for C H O : C, 70.31; H, 6.27. Found: C, 70.24; H,
3
2
34
8
6
.34.
References
(
1) (a) Wittek, M.; Všgtle, F. Chem. Ber. 1982, 115, 2533.
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21.
3
,3''',4,4',4'',4''',5',5''-Octahydroxy-1,1',2',1'',2'',1'''-quater-
(
phenyl (8b)
To a solution of 8a (4.00 g, 7.32 mmol) in CH Cl (100 mL) was
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3
Ð78¡C and 1 h at r.t. Degassed H O (50 mL) was then added drop-
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2
2
3
3
2
2
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2
(
(
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1
7
1
274, 1225, 1205, 1186, 1166, 1137, 1110, 1014, 893, 861, 814,
(
Ð1
78 cm .
(
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3
(
2
H, 6'-H, 3"-H), 5.16 (d, J = 8.2 Hz, 2 H, 5-H, 5"'-H), 4.99 (d, J =
Synthesis 1999, No. 3, 475Ð478 ISSN 0039-7881 © Thieme Stuttgart · New York

4
78
J. L. Schulte, S. Laschat
PAPER
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(
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2
(
4
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(
(
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(
(
(
(
(
Synthesis 1999, No. 3, 475Ð478 ISSN 0039-7881 © Thieme Stuttgart · New York