A convenient synthesis of biphenylene

Article abstract of DOI:10.1016/j.tetlet.2005.09.124

An efficient one-pot reaction for the synthesis of biphenylene 1 starting from biphenyl is reported. The final product was prepared from commercially available, cheap materials in moderate yet very competitive yield. Biphenyl was ortho-lithiated to 2,2′-dilithiobiphenyl 2, which was then coupled to biphenylene.

Full text of DOI:10.1016/j.tetlet.2005.09.124

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8195–8197
A convenient synthesis of biphenylene
Thomas Schaub and Udo Radius*
Institut f u¨ r Anorganische Chemie, Universit a¨ t Karlsruhe (TH), Engesserstr. 15, Geb. 30.45, D-76131 Karlsruhe, Germany
Received 5 September 2005; revised 15 September 2005; accepted 19 September 2005
Available online 7 October 2005
Abstract—An efficient one-pot reaction for the synthesis of biphenylene 1 starting from biphenyl is reported. The final product was
0
prepared from commercially available, cheap materials in moderate yet very competitive yield. Biphenyl was ortho-lithiated to 2,2 -
dilithiobiphenyl 2, which was then coupled to biphenylene.
ꢀ
2005 Elsevier Ltd. All rights reserved.
1
Biphenylene 1 was first prepared by Lothrop in 1941 by
dihalogenated derivatives of biphenyl. A method mainly
developed by Vollhardt and co-workers uses a cobalt
mediated alkyne coupling reactions of o-dialkynylbenz-
0
0
an Ullman reaction of 2,2 dibromo- or 2,2 diiodobiphen-
yl and was for many years the only known derivative of
cyclobutadiene fused to benzene. This compound, for-
mally the dibenzo-derivative of cyclobutadiene, has been
investigated thoroughly in the following years due to its
interesting chemical properties and theoretical relevance
7
enes, for example, o-diethynylbenzene IV, with other
alkynes. This procedure is valuable for substituted
biphenylene derivatives, but presumably too expensive
for the synthesis of the parent compound 1. Other ways
2
2,8
to the discussion of aromaticity. Many alternative pro-
to synthesize biphenylene rely on vacuum-pyrolysis,
tocols have been developed for its synthesis, but the
known procedures for the preparation of 1 are unsatis-
factory because they either use expensive starting mate-
rials or they afford 1 only in small amounts. A summary
of the known, preparative useful synthetic routes which
are not based on vacuum-pyrolysis is given in Scheme 1.
with the typical drawbacks of an often troublesome
preparation of starting materials, low yields, and the
problem to synthesize larger amounts of the desired
product.
We are interested in the transition metal mediated C–C
activation of biphenylene in stoichiometric as well as
3
4
9
Starting from I, II, and III, an aryne intermediate is
formed via elimination reactions, which dimerizes to
biphenylene. With the exception of the procedure start-
ing from II, the yields of biphenylene formation are gen-
erally low, and compound II has to be prepared in four
steps from o-nitroaniline in approximately 54% yield.
The standard method nowadays for the synthesis of 1
is a protocol described in Organic Synthesis starting
from commercially available anthranilic acid III, which
catalytic reactions. The NHC (N-heterocyclic carbene)
i-Pr
i-Pr
stabilized nickel complex [Ni (Im )4(COD)] (Im
=
2
1,3-di(iso-propyl)imidazole-2-ylidene), for example, is
the currently most active catalyst known for the inser-
0
tion of diphenylacetylene into the 2,2 bond of biphenyl-
ene to yield 9,10-di(phenyl)phenanthrene. Although
1
0
biphenylene is commercially available, it is expensive,
which reflects the difficulties of the preparation. Since,
we rely on a feedstock of 1 in our laboratory, we devel-
oped a new, efficient and easily achievable synthetic
approach to 1, in which commercially available, inex-
4
leads to 1 in 21%–30% yield. During this preparation,
however, explosive benzenediazonium-2-carboxylate is
an intermediate. Although it is not necessary to isolate
this substance, it is a hazardous material which should
be a driving force to replace it in the laboratory. Other
0
pensive biphenyl is directly coupled in the 2,2 -position.
Our work was inspired by the report of the coupling
6
reaction starting from VII. We report here the first syn-
5
1
6
preparations starting from V, VI, and VII employ
thesis of 1 starting directly from unsubstituted biphenyl
in a convenient one-pot procedure.
0
0
transition metal mediated coupling reactions of 2 ,2 -
Biphenyl was selectively bis-ortho-metalated using stoi-
chiometric amounts of n-BuLi and tetramethyl-ethylene-
diammine (TMEDA) and 2,2 -dilithiobiphenyl was
Keywords: Biphenylene; Biphenyl; One-pot synthesis.
*
Corresponding author. Tel.: +49 721 608 8097; e-mail: radius@aoc1.
uni-karlsruhe.de
1
1
0
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.09.124

8196
T. Schaub, U. Radius / Tetrahedron Letters 46 (2005) 8195–8197
F
Br
Br
N
N
BuLi
N
1
) nBuLi
) ZnCl2
) CuCl2
I I
NH2
Br
VII
2
3
∆
Pb(OAc)4
∆
Cu O
2
1
NH2
I
1
) (CH )(CH ) ONO
3 2 3
2)
∆ Cl CCOOH
COOH
3
1
) Li
III
1) CpCo(CO)2
2
) HgCl2
2) CF CO H
3
2
I
3)
Ag
VI
CH
I
SiMe3
+
SiMe3
CH
I
V
IV
Scheme 1. Synthetic routes to biphenylene not based on vacuum-pyrolysis methods.
Li
obtained as the TMEDA-adduct 2 in the first step of the
new developed synthesis (Scheme 2).
1
2,13
The first lithiation is preferred in ortho-position due to
inductive and solvating effects of the phenyl rings, which
affect both the transition-state and monolithiated
product. MNDO calculations performed on different
monolithiated products of biphenyl revealed an intra-
molecular stabilizing interaction between the vicinal
phenyl ring and the lithium atom in the ortho-lithiated
product, which stabilizes this compound by approxi-
mately 9.7 kcal/mol with respect to the meta and para
C
C
Li
Li
Li
A
B
Scheme 3.
The reaction product can be isolated in approximately
7% yield and was characterized H NMR spectro-
1
4
1
1
scopically. The synthesis of 1 does not require isolation
of 2. Although, we performed the synthesis of 1 in two
substituted isomers. The second lithiation step leads
0
selectively to the 2,2 -dilithiobiphenyl in good yields.
1
3,14
separate steps with isolated 2,
a one-pot procedure
This selectivity also accounts to stabilizing interactions
between vicinal phenyl rings and the lithium atoms in
conformer A, as well as an stabilizing lithium–lithium
interaction in conformer B (Scheme 3).
for the synthesis of 1 has the advantage of improved
overall yield as well as avoiding the time consuming iso-
lation of 2.
In the second step, dilithium compound 2 was coupled
with stoichiometric amounts of ZnCl2 and CuCl2
(
Scheme 4).
H C
CH3
3
N
N
Li
N
H C
CH3
n-BuLi
3
Cl
TMEDA
Zn
in Hexan
ZnCl2
CuCl2
2
Li
CH3
H C
3
in THF
in THF
N
H C
CH3
3
Zn
Cl
2
3
1
Scheme 2.
Scheme 4.

T. Schaub, U. Radius / Tetrahedron Letters 46 (2005) 8195–8197
8197
The first step of this reaction requires the addition of
dried and refluxed over sodium (THF, TMEDA, toluene,
and pentane) and N . Solvents were distilled at atmo-
spheric pressure prior to use. N-BuLi (192.5 mL,
14 mmol: 16% in hexane) was added at room temperature
to a stirred solution of biphenyl (20.0 g, 129 mmol) in dry
TMEDA (47.1 mL, 314 mmol). The solution was stirred
for 3 days at room temperature and all volatiles were
removed afterwards in vacuo. The red residue was
suspended in THF (400 mL) and a solution of anhydrous
anhydrous ZnCl to a solution of 2 in THF at ꢀ78 ꢁC,
2
2
which affords the corresponding zinc organyl 3. Further
3
addition of anhydrous CuCl at ꢀ78 ꢁC leads to the coup-
2
6
ling of 3 to biphenylene 1. After this step, the reaction
mixture was hydrolyzed and the product was extracted
with toluene. The crude product was recrystallized from
pentane and purified by vacuum sublimation to give
analytically pure 1 in the form of an off white, micro-
ZnCl (41.8 g, 306 mmol) dissolved in THF (280 mL) was
2
1
2
crystalline solid in 37% yield. For the two-step synthe-
sis, the yield was significantly lower (25–27%), mainly
due to losses during the purification of 2.
added at ꢀ78 ꢁC. The resulting mixture was stirred for
90 min at ꢀ78 ꢁC, anhydrous CuCl
2
(51.8 g, 386 mmol)
was added, and the resulting suspension was stirred for 3 h
at ꢀ78 ꢁC and 1 day at room temperature to give a deep
green solution. This solution was hydrolyzed with 4 M
hydrochloric acid (267 mL), and the product was extracted
twice with toluene (2 · 500 mL). The combined organic
phases were washed twice with water (200 mL), dried over
anhydrous sodium sulfate and all volatile material were
removed in vacuo. The product was extracted with
pentane (500 mL) from the remaining residue and the
extract was stored at ꢀ40 ꢁC overnight to give a yellowish
precipitate, which was filtered off at ꢀ40 ꢁC. The mother
liquid was concentrated to 50–70 mL and stored at ꢀ40 ꢁC
for a second crop of crude product. The combined
In conclusion, we enclosed an efficient one-pot reaction
of biphenylene 1 starting from unsubstituted biphenyl.
This reaction can be performed with commercially avail-
able, inexpensive starting materials to give biphenylene 1
in moderate yet competitive yield. This procedure is suit-
able for a 10–20 g scale preparation of biphenylene in
short time.
Acknowledgements
ꢀ3
fractions were sublimed in vacuo (10 Torr) at 150 ꢁC
to afford 7.40 g (37%) biphenylene as an off white
Financial support of the Fonds der Chemischen Indust-
rie and the Deutsche Forschungsgemeinschaft is grate-
fully acknowledged.
substance. C12
H
8
[152.2 g/mol]. Calcd (found): C, 94.70
+
(
94.37); H, 8.78 (8.68). EI/MS m/z (%): 152 (100) = [M ],
6 (20) = [M] . H NMR (C
2+
1
7
6
D
6
): d = 6.40 (m, 4H, Ar–
): d = 118.50
Aryl–C ), 128.90 (Aryl–C ), 152.70 (Aryl–C ).
1
3
6 6
H), 6.55 (d, 4H, Ar–H). C NMR (C D
(
i
o
m
0
References and notes
13. Synthesis of 2.2 -dilithiobiphenyl 2: N-BuLi (192.5 mL,
14 mmol: 16% in hexane) was added at room temperature
3
1
2
. Lothrop, W. C. J. Am. Chem. Soc. 1941, 63, 1187.
. See, for example: (a) Shepherd, M. K. Cyclobutarenes—
The Chemistry of Benzocyclobutene, Biphenylene, and
Related Compounds; Elsevier: Amsterdam, 1991; (b) Toda,
F.; Garatt, P. Chem. Rev. 1992, 92, 1685.
to a stirred solution of biphenyl (20.0 g, 129 mmol) in dry
TMEDA (47.1 mL, 314 mmol). The solution was stirred
for 3 days at room temperature to give a yellow precipitate
and a red solution. The precipitate was filtered off, washed
twice with hexane (20 mL), and dried in vacuo. The filtrate
was stored at ꢀ40 ꢁC overnight to obtain a crop of yellow
crystals of the TMEDA adduct (2ÆTMEDA) of 2. These
were filtered off at ꢀ78 ꢁC, washed with cold hexane
(ꢀ78 ꢁC, 60 mL), and dried in vacuo. The overall yield of
3
. Campbell, C.-D.; Rees, C. W. J. Chem. Soc. (C) 1969,
7
42.
4
. Logullo, F. M.; Seits, A. H.; Friedman, L. Org. Synth.
Coll. Vol. 5, 1973, 54.
1
5
6
. Wittig, G.; Herwig, W. Chem. Ber. 1954, 87, 1511.
. Iyoda, M.; Kabi, S. M. H.; Vorashinga, A.; Kuwatani, Y.;
Yoshidi, M. Tetrahedron Lett. 1998, 39, 5393.
the combined fractions is 24.4 g (47%). H NMR (C D ):
6
6
d = 1.76 (s, 8H, N–CH
4H, CAr–H ), 7.49 (m, 2H, CAr–H
H ).
p
2
), 1.83 (s, 24H, N–(CH
3 2
) ), 7.18 (s,
m
o
), 8.48 (q, 2H, CAr–
7
. Berris, B. C.; Lai, Y. H.; Vollhardt, K. P. C. J. Chem. Soc.,
Chem. Commun. 1982, 953.
14. Synthesis of biphenylene 1 starting from 2ÆTMEDA: Com-
plex 2 Æ TMEDA (24.4 g, 61.2 mmol) was dissolved in
200 mL THF at ꢀ78 ꢁC and a solution of anhydrous
8
. (a) Brown, R. F. C.; Browne, N. R.; Coulsten, K. J.;
Eastwood, F. W.; Irwine, M. J.; Pullin, D. E.; Wiersum,
U. E. Aust. J. Chem. 1989, 42, 1321; (b) Brown, R. F. C.;
Coulsten, K. J.; Eastwood, F. W.; Vogel, K. Aust. J.
Chem. 1988, 41, 1687; (c) Suhr, H.; Henne, P. Liebigs Ann.
Chem. 1977, 1610; (d) Barry, M.; Brown, F. C.; Eastwood,
F. W.; Gunawaranda, D. A.; Vogel, K. Aust. J. Chem.
ZnCl (19.9 g, 145 mmol) in 180 mL THF was added.
2
After addition, a white precipitate started to form and
after 90 min stirring, anhydrous CuCl (19.9 g, 148 mmol)
2
was added. The mixture was stirred for another 3 h at
ꢀ78 ꢁC and for 1 day at room temperature. Afterwards it
was hydrolyzed with 4 M hydrochloric acid (127 mL), and
the product was extracted with toluene (3 · 250 mL). The
combined extracts were washed twice with water (150 mL)
and dried over anhydrous sodium sulfate. All volatile
material was removed in vacuo to obtain a dark yellow
crude product. Pure biphenylene was obtained by subli-
1
984, 37, 1643.
9
. Schaub, T.; Radius, U. Chem. Eur. J. 2005, 11, 5024.
1
1
1
0. For example: Aldrich no. 321958; 100 mg: 45.10€ (catalog
2
005–2006).
1. Neugebauer, W.; Kos, A. J.; von Rague Schleyer, P. J.
Organomet. Chem. 1982, 228, 107.
2. Synthesis of biphenylene 1: All air/moisture sensitive
manipulations were performed using standard Schlenk-
ꢀ
3
mation at 150 ꢁC in vacuo (10 Torr) on a water cooled
sublimation finger to afford 5.30 g (55%) of an off white
solid.
2
line (N ) and dry-box (Ar) techniques. Solvents were pre-