Synthesis of 1-(2-ethynyl-6-methylphenyl)- and 1-(2-ethynyl-6-methoxyphenyl)-naphthalene and their cyclization

Article abstract of DOI:10.1016/j.tetlet.2007.07.105

A Suzuki cross-coupling reaction of hindered 2-bromo-1-trimethylsilylethynylbenzenes with 1-naphthaleneboronic acid yielding (2-ethynylphenyl)naphthalenes has been achieved. Their subsequent cyclization was carried out, giving benzo[c]phenanthrenes, without the use of photochemical procedures.

Full text of DOI:10.1016/j.tetlet.2007.07.105

Tetrahedron Letters 48 (2007) 6814–6816
Synthesis of 1-(2-ethynyl-6-methylphenyl)- and
1-(2-ethynyl-6-methoxyphenyl)-naphthalene and their cyclization
*
ˇ
´
Jan Storch, Jan Cermak and Jindrˇich Karban
Institute of Chemical Process Fundamentals, AS CR, Rozvojova´ 135, CZ-16502 Prague 6, Czech Republic
Received 2 April 2007; revised 29 June 2007; accepted 12 July 2007
Available online 26 July 2007
Abstract—A Suzuki cross-coupling reaction of hindered 2-bromo-1-trimethylsilylethynylbenzenes with 1-naphthaleneboronic acid
yielding (2-ethynylphenyl)naphthalenes has been achieved. Their subsequent cyclization was carried out, giving benzo[c]phenanth-
renes, without the use of photochemical procedures.
Ó 2007 Elsevier Ltd. All rights reserved.
Interest in the preparation of polycyclic aromatic
hydrocarbons (PAHs), which are widely distributed in
the environment, has been stimulated by the desire to
understand their involvement in the mechanisms of
carcinogenesis and also by the discovery of sophisti-
cated systems such as fullerenes or nanotubes having
extraordinary properties. Numerous synthetic proce-
dures for the construction of large polycyclic aromatic
systems have been described in the literature.1 How-
ever, there are not many studies that deal with the
preparation of differently monosubstituted benzo[c]phen-
anthrenes. Efforts have been devoted to the synthesis
of compounds such as 3-hydroxy-,2 4-hydroxy3 and
6-methoxybenzo[c]phenanthrene.4 An article concern-
ing only non-photochemical procedures for the synthe-
sis of 1-hydroxybenzo[c]phenanthrene was published by
Newman in 1964.5 Herein we report a metal-induced
carbocyclization6 of alkynylated phenyl-naphthalenes
for the preparation of 1-hydroxybenzo[c]phenan-
threnes.
CH3
CH3
CH3
Br
Br
I
ii, iii
i
NH2
NH2
5b
Scheme 1. Reagents and conditions: (i) Br2, SiO2, CHCl3; (ii) NaNO2,
H2SO4, 10 °C, (iii) KI, 10 °C ! 80 °C, (5b): 61%.
2-Bromo-1-trimethylsilylethynylbenzenes 1 (Scheme 2),
to be used in the Suzuki coupling reactions with naph-
thaleneboronic acid, were prepared by Sonogashira cou-
pling with trimethylsilylacetylene and compounds 5a–c
under standard conditions.
The key step in the synthesis of benzo[c]phenanthrenes
was the Suzuki coupling of an appropriate bromobenz-
ene 1 with 1-naphthaleneboronic acid under palla-
dium/2-(20,60-dimethoxybiphenyl)dicyclohexylphosphine
(L) catalysis under conditions described recently.9 The
reaction led to phenyl-naphthalenes 2 in high yields.
Their carbocyclization catalyzed by PtCl2 followed a
6-endo pathway with concomitant cleavage of the tri-
methylsilyl group to give benzo[c]phenanthrenes 3.10
The electrophilic cleavage of the silicon–carbon bond
during the reaction is probably due to the H+/H2O sys-
tem. Traces of acid (HCl) were probably derived from
PtCl2 prepared from H2PtCl6, and water may have orig-
inated from undried toluene. The reaction did not occur
with methyl substituted phenylnaphthalene 2b. 1-Meth-
oxybenzo[c]phenanthrene 3c was demethylated using
BBr3 to afford 1-hydroxybenzo[c]phenanthrene 3d.11
2-Bromo-1-iodobenzenes 5a and 5c were prepared
according to literature7 procedures. 2-Bromo-1-iodo-3-
methylbenzene 5b was prepared starting from m-tolu-
idine, according to Scheme 1. Selective bromination in
8
the presence of SiO2 gave 2-bromo-m-toluidine in high
yield, which was then converted into the corresponding
iodide by means of the diazonium salt.
*
Corresponding author. Fax: +420 220920661; e-mail: storchj@
icpf.cas.cz
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.105

J. Storch et al. / Tetrahedron Letters 48 (2007) 6814–6816
6815
R
R
ii
iii
R
TMS
Br
TMS
i
1a R = H
1b R = CH3
1c R = OCH3
2a R = H
2b R = CH3
2c R = OCH3
3a R = H
3b R = CH3
3c R = OCH3
iv
3d R = OH
R
I
5a R = H
5b R = CH3
5c R = OCH3
Br
Scheme 2. Reagents and conditions: (i) TMS–C„CH, PdCl2(PPh3)2, CuI, Et3N, rt, (1a): 98%, (1b): 89%, (1c): 98%; (ii) 1-naphthaleneboronic acid,
L, Pd2(dba)3ÆCHCl3, K3PO4, toluene, 90 °C, (2a): 95%, (2b): 90%, (2c): 90%; (iii) PtCl2, toluene, 90 °C, (3a): 86%, (3b): 0%, (3c): 80%; (iv) BBr3,
CH2Cl2, rt, (3d): 88%.
OTf
H3C
Ar
H3C
H3C
not
TFA or TfOH
CH2Cl2, r. t.
Ar
Ar
4
Ar =
OCH3
Scheme 3. Attempts for electrophilic cyclization.
6
Attempts to catalyze cyclization of 2b with InCl3 or
References and notes
6
PdCl2(PhCN)2/2AgBF4 did not provide any detectable
1. Harvey, R. G. Curr. Org. Chem. 2004, 8, 303–
323.
2. (a) Kumar, S. J. Org. Chem. 1997, 62, 8535–8539; (b)
Pataki, J.; Raddo, Di P.; Harvey, R. G. J. Org. Chem.
1989, 54, 840–844.
3. Bijay, M.; Shantu, A. J. Org. Chem. 1990, 55, 4478–
4480.
4. Mallory, F. B.; Rudolph, M. J.; Oh, S. M. J. Org. Chem.
1989, 54, 4619–4626.
amount of the desired product. The reaction failed prob-
ably due to steric influences. To support this conclusion,
we attempted electrophilic cyclization of compound 4,
where Ar was an electron-rich p-methoxyphenyl group
(Scheme 3), which provided resonance stabilization of
the positive charge at the b-carbon and would thus lead
to preferential protonation at the a-carbon.12 Treatment
of 4 with TfOH or TFA produced the corresponding
vinyl ester as the only isolable product.
5. Newman, M. S.; Blum, J. J. Am. Chem. Soc. 1964, 86,
503–507.
6. Mamane, V.; Hannen, P.; Furstner, A. Chem. Eur. J. 2004,
¨
In summary, we have prepared 1-hydroxybenzo[c]phen-
anthrene via an atom economic cyclization method
in three simple steps compared to Newman method5
which involved eight steps starting from diethyl
benzhydrylmalonate.
10, 4556–4575.
7. (a) Tunney, S. E.; Stille, J. K. J. Org. Chem. 1987, 52, 748–
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Acknowledgment
9. Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald,
S. L. J. Am. Chem. Soc. 2005, 127, 4685–4696.
10. A solution of phenyl-naphthalene 2c (1 g, 3.0 mmol) and
PtCl2 (80 mg, 0.3 mmol) in toluene (10 mL) was stirred for
20 h at 90 °C. The solvent was evaporated and the residue
The support of the Ministry of Education, Youth and
Sport of the Czech Republic (Grant No. LC06070) is
gratefully acknowledged.

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J. Storch et al. / Tetrahedron Letters 48 (2007) 6814–6816
1
was purified by flash silica gel column chromatography
using 20% acetone–hexane as eluent to give 1-meth-
oxybenzo[c]phenanthrene 3c as a yellow solid (0.6 g, 78%).
1H NMR (500 MHz; CDCl3) d 3.84 (s, 3H), 7.16 (dd,
J = 2.0, 7.5 Hz, 1H), 7.44–7.63 (m, 4H), 7.79 (AB, J =
8.4 Hz, 1H), 7.82 (AB, J = 8.5 Hz, 1H), 7.85 (AB, J =
8.4 Hz, 1H), 7.94 (AB, J = 8.5 Hz, 1H), 7.95–7.97 (m, 1H),
8.16–8.18 (m, 1H); 13C NMR (75 MHz; CDCl3) d 156.6,
135.1, 132.4, 131.6, 131.0, 130.1, 127.6, 127.05, 127.02,
127.0, 126.6, 126.0, 125.8, 125.4, 123.4, 120.7, 120.1, 107.4,
54.6; EI-MS: m/z 258 (100% M+), 242, 226, 213, 121, 113,
106, 101, 94. Anal. calcd for C19H14O: C, 88.34; H, 5.46;
O, 6.19. Found: C, 88.06; H, 5.56; O, 6.23%.
11. Spectroscopic data for 3d: H NMR (300 MHz; CDCl3) d
5.56 (br s, 1H), 7.22 (dd, J = 2.7, 6.3 Hz, 1H), 7.60–7.90
(m, 4H), 7.71 (AB, J = 8.5 Hz, 1H), 7.83 (AB, J = 8.5 Hz,
1H), 7.84 (AB, J = 8.5 Hz, 1H), 7.92 (AB, J = 8.5 Hz,
1H), 8.00 (m, 1H), 8.17 (m, 1H); 13C NMR (75 MHz;
CDCl3) d 152.6, 135.0, 132.9, 131.8, 128.5, 128.0, 127.8,
127.7, 127.5, 127.4, 126.7, 126.3, 126.2, 126.1, 124.0, 120.4,
118.1, 113.1; EI-MS: m/z 243 (100%, M+ꢀH), 213, 121,
106, 94. Anal. calcd for C18H12O: C, 88.50; H, 4.95; O,
6.55. Found: C, 88.32; H, 4.99; O, 6.61%.
12. Goldfinger, M. B.; Crawford, K. B.; Swager, T. M. J. Am.
Chem. Soc. 1997, 119, 4578–4593.