Efficient synthesis of 3,3′,5,5′-tetra(p-X-phenylethynyl)biphenyl (X: NMe2; OMe) by homocoupling of 1-bromo-3,5-di(p-X-phenylethynyl)benzene or by heterocoupling of 3,3′,5,5′-tetraethynylbiphenyl with p-X-phenylbromobenzene with nickel or palla

Article abstract of DOI:10.1016/j.tet.2009.01.036

The conjugated 3,3′,5,5′-tetra(p-X-phenylethynyl)biphenyl derivatives were efficiently obtained by homocoupling of 1-bromo-3,5-di(p-X-phenylethynyl)benzene mediated by zero-valent nickel complexes. The 1-bromo-3,5-di(p-X-phenylethynyl)benzene was previous

Full text of DOI:10.1016/j.tet.2009.01.036

Tetrahedron 65 (2009) 2551–2555
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient synthesis of 3,30,5,50-tetra(p-X-phenylethynyl)biphenyl
(X: NMe2; OMe) by homocoupling of 1-bromo-3,5-di(p-X-phenylethynyl)
benzene or by heterocoupling of 3,30,5,50-tetraethynylbiphenyl with p-X-
phenylbromobenzene with nickel or palladium complexes, respectively
*
´
J. Gonzalo Rodrıguez , Teresa Laparra
´
´
Departamento de Qu´ımica Organica, Facultad de Ciencias, Universidad Autonoma, Cantoblanco 28049-Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
The conjugated 3,30,5,50-tetra(p-X-phenylethynyl)biphenyl derivatives were efficiently obtained by
homocoupling of 1-bromo-3,5-di(p-X-phenylethynyl)benzene mediated by zero-valent nickel complexes.
The 1-bromo-3,5-di(p-X-phenylethynyl)benzene was previously prepared by heterocoupling between
1-bromo-3,5-di(ethynyl)benzene and p-X-iodobenzene (X: NMe2; OMe) catalysed by the palladium/
copper system in good yield. The necessary 1-bromo-3,5-di(ethynyl)benzene was obtained by hetero-
coupling between 1,3,5-tribromobenzene and 2-methyl-3-butyn-2-ol catalysed by palladium and suc-
cessive treatment with sodium hydroxide in dry toluene, in good yield.
The same 3,30,5,50-tetra(p-X-phenylethynyl)biphenyl (X: NMe2; OMe) derivatives were alternatively
synthesised in highest yield by heterocoupling between 3,30,5,50-tetra(ethynyl)biphenyl and p-X-bro-
mobenzene (X: NMe2; OMe) catalysed by palladium in excellent yields. Previously, 3,30,5,50-tetra(ethy-
nyl)biphenyl was obtained in practically quantitative yield by homocoupling of 1-bromo-3,5-di-
[4-(2-methyl-3-butyn-2-ol)] benzene mediated by the zero-valent nickel complex to the 3,30,5,50-tet-
ra{di[4-(2-methyl-3-butyn-2-ol)]}biphenyl followed the treatment with sodium hydroxide.
Ó 2009 Published by Elsevier Ltd.
Article history:
Received 24 September 2008
Received in revised form 3 December 2008
Accepted 8 January 2009
Available online 14 January 2009
Keywords:
Biphenyl derivatives
3,30,5,50-Tetra(ethynylphenyl)biphenyls
Zero-valent nickel catalyst
Palladium catalyst
Sonogashira reaction
1. Introduction
Thus, the homocoupling of haloaryl derivatives mediated by
the zero-valent nickel complex affords efficiently the corre-
Symmetric biaryls were usually prepared by the Ullman
reaction, which requires an aryl halide in equimolar amount with
copper powder and temperatures up to 200 ꢀC.1 Methods for the
synthesis of biaryl or oligoaryl compounds with different proper-
ties were reported.2 Actually, the coupling reaction of organic
halides can be catalysed by transition organometallic nucleophiles
in moderated temperatures and is an attractive method for the
sponding biaryl under mild conditions. Semmelhack et al.7 use
stoichiometric amounts of bis-(1,5-dichlorooctadiene)nickel(0) in
N,N-dimethylformamide. In general, the zero-valent nickel com-
plexes were prepared in situ by reduction of Ni[(PPh3)2]Cl2 with
Zn in presence of tetrabutylammonium iodide in tetrahydro-
furan.8,9
In the same way, the homocoupling of a conveniently substituted
halobenzene to biphenyls was selectivity achieved by a palladium
catalyst, sodium carbonate and TBAB, all supported on activated
carbon.10
We have analysed different zero-valent nickel complexes for
the homocoupling of haloarenes.8 Thus, the zero-valent tetrakis-
(triphenylphosphine)nickel was used in the intramolecular cycli-
sation between an aryl halide and an exocyclic double bond. On the
basis of the secondary products’ identification, a mechanism of
reaction has been proposed.8 The first step is the oxidative addition
synthesis of
s
C–C bonds.3
Synthesis of conjugated p-(ethynylphenylethynyl)nbenzene
derivatives was recently reported, showing fluorescence emission
properties.4
The 3,30,5,50-tetra(p-X-phenylethynyl)biphenyls (X: NMe2;
OMe) of controlled structure and dimension were synthesised by
two successive catalysed methods: (i) homocoupling of the ap-
propriate halophenyl derivative mediated by in situ recently
prepared zero-valent nickel complexes;5 and (ii) Sonogashira pal-
ladium/copper catalyst heterocoupling between the corresponding
ethynylbenzene and the appropriate halophenyl derivative.6
of the aryl halide to the zero-valent nickel complex as L3Ni–ArX
complex, followed by the metathesis to the L2XNi–Ar complex
and the -nickel coordination to the double bond giving the
p
s
s
effective cyclisation and hydride nickel halide species in solution of
THF (HNiClL2).
* Corresponding author. Tel.: þ34 914974715; fax: þ34 914973966.
´
E-mail address: gonzalo.rodriguez@uam.es (J.G. Rodrıguez).
0040-4020/$ – see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tet.2009.01.036

2552
J.G. Rodr´ıguez, T. Laparra / Tetrahedron 65 (2009) 2551–2555
The reductive elimination of the formed species of arylnickel(II)
diethynylbenzene (2) and p-(N,N-dimethylamino)-iodobenzene in
presence of dichloro bis(triphenylphosphine) palladium (5 mol %)
and cuprous iodide (2 mol %) in triethylamine at 60 ꢀC. Compound 3
was isolated as a brown solid, mp >300 ꢀC, in good yield (67%),
Scheme 2.
affords the biaryl compound and regenerates the nickel(0) species.10
Tsou and Kochi11 proposed a radical mechanism, which implies
the oxidative addition of the haloarene ArX to the Ni(I)X in-
termediate giving the ArNi(II)X2 complex.
We now report the synthesis of conjugated 3,30,5,50-tetra(p-X-
phenylethynyl)biphenyls (X: NMe2; OMe) by homocoupling
reaction of conjugated halophenyl derivatives mediated by zero-
valent nickel and palladium complexes.
Finally, the homocoupling of 1-bromo-3,5-(p-N,N-dimethyl-
aminophenylethynyl)benzene (3) was catalysed by zero-valent
nickel complex in THF at room temperature giving 5 as a yellow oil,
with good yield (65%).
The zero-valent nickel complex catalyst was always used in
stoichiometric molar ratio with the bromo derivative and was
prepared in situ by reaction between dichloro bis(triphenylphos-
phine) nickel with powder of zinc as the reductive agent and tetra-
butylammoniumiodide as a phase transferagent, in tetrahydrofuran
as solvent.
2. Results and discussion
The synthesis of the 3,30,5,50-(tetraethynyl-p-X-phenyl)biphenyl
compounds has been undertaken as partially conjugated dendron
structures by combining the catalysed homo and heterocoupling
reactions.
2.2. Synthesis of 3,30,5,50-tetra(p-methoxy)(phenylethynyl)-
2.1. Synthesis of 3,30,5,50-tetra(p-N,N-dimethylamino)
biphenyl (6)
(phenylethynyl)biphenyl (5)
Compound 6 was obtained by the homocoupling reaction of
1-bromo-3,5-(p-methoxyphenylethynyl)benzene (4) catalysed by
zero-valent nickel complex in THF, at room temperature, as
a yellow oil in good yield (61%).
Compound 3 was prepared by heterocoupling reaction between
2-methyl-3-butyn-2-ol and 1,3,5-tribromobenzene (2.4 molar
ratio, respectively) in triethylamine, in the presence of dichloro
bis(triphenyl)phosphine palladium and cuprous iodide, at room
temperature. After chromatography, 1-bromo-3,5-di[4-(2-methyl-
3-butyn-2-ol)]benzene (1) was isolated as yellow solid, mp
95–97 ꢀC, in moderated yield (56%),12 Scheme 1.
Compound 1 was treated with catalytic amount of anhydrous
powder of sodium hydroxide in dry toluene at the reflux temper-
ature to give 1-bromo-3,5-di(ethynyl)benzene (2) as a pale-yellow
solid, mp 102–105 ꢀC, in practically quantitative yield, Scheme 1.
The biphenyl 5 was prepared by homocoupling of 1-bromo-
3,5-di(p-N,N-dimethylaminophenylethynyl)benzene (3) catalysed
by the zero-valent nickel complex in stoichiometric amount,
Scheme 2.
Compound
4 was obtained by heterocoupling between
1-bromo-3,5-diethynylbenzene and p-(dimethoxy)-iodobenzene
in presence of the palladium–copper system in triethylamine at
40 ꢀC as a brown solid, mp >300 ꢀC, in good yield (87%).
Alternatively the yield in the synthesis of the 3,30,5,50-tetra-
(substituted)biphenyl (5, 6) was improved by heterocoupling
reaction between 3,305,50-tetra(ethynyl)biphenyl (8) and p-(X)-
iodobenzene catalysed by dichloro bis(triphenylphosphine)
palladium and cuprous iodide system in diethylamine.
2.3. Synthesis of 3,30,5,50-tetra(ethynyl)biphenyl (8)
Now,
1-bromo-3,5-di(p-N,N-dimethylaminophenylethynyl)-
In this way, compound 1 was obtained by heterocoupling
benzene (3) was prepared by heterocoupling between 1-bromo-3,5-
between 1,3,5-tribromobenzene and 2-methyl-3-butyn-2-ol, in
HO
H
Br
ii.
i.
Br
Br
Br
Br
1, 70%
i. 2-methyl-3-butyn-2-ol;
Cl2Pd(Ph3P)2 (5 % molar),
2, quantitative
ii. NaOH powder catalyst,
H
at toluene reflux.
HO
Cu2I2 (2 % molar).
Alcohol:TBB, 2.4 mol. ratio
Scheme 1.
R
R
R
H
R
I
ii.
Br
Br
i.
ii. Cl2Ni(PPh3)2,
Zn/ Bu4IN/THF
2
H
i. Cl2Pd(PPh3)2, 5 % molar
Cu2I2, Et3N, 2 % molar
2:R-Ph-I, 0.67 molar ratio
R, NMe2, 3, 67 %;
R, OMe, 4, 87 %.
R, NMe2, 5, 65 %
R, OMe, 6, 61 %
R
R
R
Scheme 2.

J.G. Rodr´ıguez, T. Laparra / Tetrahedron 65 (2009) 2551–2555
OH
2553
HO
OH
H
H
H
H
Br
H
OH
iii.
ii.
ii. Cl2Ni(PPh3)2;
THF/ BuNH4I/ Zn
Br
i.
NaOH, toluene,
reflux
Br
Br
7
8
1
i. Cl2Pd(PPh3)2;
Cu2I2/ Et3N
OH
HO
Scheme 3.
OH
0.43 molar ratio, respectively, catalysed by dichloro bis(triphe-
nylphosphine) palladium and cuprous iodide in triethylamine.12
The monobromo derivative 1 was isolated as a white solid, mp
52–54 ꢀC, in good yield (70%), Scheme 3.
The homocoupling reaction of the monobromo derivative 1 in
presence of the zero-valent nickel complex in THF, at room tem-
perature, affords the biphenyl derivative 7 as a white solid, mp
191–193 ꢀC, in excellent yield (95%), Scheme 3.
Now, 3,30,5,50-tetra(ethynyl)biphenyl was obtained by treat-
ment of the tetrasubstituted biphenyl 7 with catalytic anhydrous
powdered sodium hydroxide, in dry toluene at the reflux temper-
ature, as a yellow solid, which was crystallised in hexane, mp
189–191 ꢀC, in good yield (87%).
Compound 8 serves to prepare the 3,30,5,50-tetra(p-X-phenyl)-
biphenyl by heterocoupling with the appropriate p-X-iodobenzene
catalysed by the palladium/copper system.
3. Conclusions
The homocoupling of 1-bromo-3,5-di(p-X-phenylethynyl)-
benzene derivatives to the corresponding biphenyl derivatives can
be carried out in good yield with stoichiometric catalytic amounts
of the nickel zero-valent complex. The presence of the catalyst in
lowest amounts gives minor yield in the homocoupled product and
hence the zero-valent nickel catalyst complex was not regenerated
during the reaction.
Alternatively, highest yield for the same 3,5,30,50-tetra(p-X-phe-
nylethynyl)biphenyl derivatives can be obtained by heterocoupling
between 3,5,30,50-tetra(ethynyl)biphenyl and p-X-iodobenzene in
presence of palladium catalyst (5 mol %) and cuprous iodide
(2 mol %) in excellent yields. Previously, the 3,5,30,50-tetra(ethy-
nyl)biphenyl intermediate (8) was obtained by homocoupling of
1-bromo-3,5-di(2-methyl-3-butyn-2-ol)benzene to the biphenyl
intermediate 7 in excellent yield, and successive careful treatment
with sodium hydroxide in toluene, at the reflux temperature, in
practically quantitative yield.
2.4. Synthesis of 3,30,5,50-Tetra[p-(N,N-dimethylamino-
phenyl)biphenyl (5) from 8
Thus, compound 5 was obtained by heterocoupling between
3,30,5,50-tetra(ethynyl)biphenyl (8) and p-(N,N-dimethylamino)-
iodobenzene, in triethylamine, catalysed by dichloro bis(triphen-
ylphosphine) palladium and cuprous iodide. Compound 5 was
isolated as yellow oil, in excellent yield (93%). The analytical and
spectral data coincide with the same compound obtained by
homocoupling of 3 with the zero-valent nickel complex. Hence,
highest yield was obtained for the heterocoupling catalysed
reaction.
4. Experimental
4.1. General
Melting points were determined in open capillaries using
a Reichert hot-stage microscope and are uncorrected. IR spectra of
solids were recorded as KBr pellets and IR spectra of oils were
recorded as thin films on NaCl plates with a Bruker Vector 22
spectrophotometer, and the wave numbers are given in cmꢁ1 1H
.
and 13C NMR spectra were recorded at 200 and 75 MHz,
respectively, on a Bruker Aspect spectrometer, chemical shifts are
2.5. Synthesis of 3,30,5,50-tetra(p-methoxyphenyl-
ethynyl)biphenyl (6) from 8
given in d, using TMS as an internal reference and constant J values
are given in hertz, the solvent is CDCl3. Mass spectra were recorded
on a VG Autospec spectrometer at 70 eV. Elemental analyses were
performed with a LECO CHN-900. Yields are given after silica gel
column chromatography separation.
Compound 6 was obtained by heterocoupling of 3,30,5,50-tetra-
(ethynyl)biphenyl (8) with p-iodoanisole, in triethylamine, cata-
lysed by dichloro bis(triphenylphosphine) palladium and cuprous
iodide, as yellow oil, in good yield (83%), Scheme 4.
4.2. Synthesis of 3,30,5,50-tetra(p-N,N-dimethylamino-
phenylethynyl)biphenyl (5)
R
R
4.2.1. 3,5-Bis(3-methyl-1-butyn-3-ol)-1-bromobenzene (1)
H
H
H
H
A mixture of 2-methyl-3-butyn-2-ol (64.5 mg, 0.77 mmol), tri-
bromobenzene (100 mg, 0.32 mmol), Pd[(PPh3)2]Cl2 (5 mol %) and
Cu2I2 (2% mol) in toluene (20 mL) was stirred at room temperature
for 12 h (monitored by TLC). Then, a saturated aqueous solution of
ammonium chloride (30 ml) and a little amount of KCN (5 mg)
were added, and the organic layer was separated and dried on
sodium sulfate. Finally solvent was removed and compound 1 was
isolated as a white solid, mp 52–54 ꢀC (401.2 mg, 70%).12
i.
I
R
8
i. Cl2Pd(PPh3)2 (5 % mol.)
Cu2I (2 % mol.), Et3N
R, NMe2, 5, 88 %.
R, OMe, 6, 83 %.
R
R
1H NMR (CDCl3): 7.44 (d, 2H, J¼1.62 Hz, H-2, H-6), 7.34 (t, 1H,
J¼1.62 Hz, H-4), 2.89 (br s, 2H, 2-OH), 1.57 (s, 12H, 4-Me).
Scheme 4.

2554
J.G. Rodr´ıguez, T. Laparra / Tetrahedron 65 (2009) 2551–2555
4.2.2. 1-Bromo-3,5-di(ethynyl)benzene (2)
(10 ml). After solvent was removed the residual solid obtained was
purified by silica gel column chromatography (hexane/dichloro-
methane, 2:1) giving 4 (68.48 mg, 87%) as a brown solid mp
>300 ꢀC.
Compound 1 (100 mg, 0.5 mmol) was treated with a catalytic
amount of powder sodium hydroxide in dry toluene at reflux
temperature for 2 h giving 2 as a pale-yellow solid, mp 102–105 ꢀC,
in practically quantitative yield.
IR (KBr): 3345 (^CH), 3029 (ArC–H), 2248 (C^C), 1268 (C]C),
825 and 715 (1,3,5-trisubst.), 686 (C–Br). 1H NMR (CDCl3): 7.60 (s,
2H, H-2, H-6), 7.52 (s,1H, H-4), 3.13 (s, 2H, ^C–H). 13C NMR (CDCl3):
135.1 (C-2, C-6), 134.2 (C-1), 124.2 (C-3, C-5), 121.8 (C-4), 81.1 (^C–
Ph), 79.3 (^C–H). Anal. Calcd for C10H5Br (205.05): C, 58.58; H,
2.46. Found: C, 58.65; H, 2.52.
4.3.2. 3,30,5,50-Tetra(p-methoxyphenylethynyl)biphenyl (6)
A
solution of Cl2Ni(PPh3)2 (92.12 mg, 0.14 mmol), Bu4NI
(51.7 mg, 0.14 mmol), powder of Zn (14 mg, 0.21 mmol) in dry THF
was stirred for 30 min and then was added 4 (56.08 mg, 0.14 mmol)
and stirred for 12 h at room temperature. Solvent was removed and
the residual brown oil was purified by silica gel column chroma-
tography giving 6 (61.7 mg, 61%) as a yellow oil.
4.2.3. 1-Bromo-3,5-di(p-N,N-dimethylamino-
phenylethynyl)benzene (3)
Anal. Calcd for C48H34O4 (674.79): C, 85.44; H, 5.08. Found: C,
85.27; H, 5.18.
To a mixture of 2 (41.01 mg, 0.20 mmol) and dichloro bis-
(triphenylphospine) palladium (15 mg, 0.061 mmol, 5 mol %) and
cuprous iodide (2 mol %) was added a solution of p-N,N-dimethyl-
amino-iodobenzene (61.5 mg, 0.30 mmol) in freshly distilled tri-
ethylamine andstirred at60 ꢀC for24 h. Themixturewastreatedwith
a saturated aqueous solution of ammonium chloride (20 ml) and
a little amount of potassium cyanide (5 mg) and extracted with
dichloromethane. After solvent was removed the residual solid
obtained was purified by silica gel column chromatography (hexane/
dichloromethane, 2:1) giving 3 (55.66 mg, 67%) as a brown solid mp
>300 ꢀC.
4.4. Synthesis of 3,5,30,50-tetra(ethynyl)biphenyl (8)
4.4.1. 3,305,50-Tetra(3-methyl-1-butyn-3-ol)biphenyl (7)
A mixture of Cl2Ni(PPh3)2 (480 mg, 0.72 mmol), tetrabutyl-
ammonium iodide (267 mg, 0.72 mmol) and powder of Zn
(68.8 mg, 1.1 mmol), was stirred at room temperature for 30 min.
Then, a solution of 1-bromo-3,5-di(3-methyl-1-butyn-3-ol)benzene
(4) (240 mg, 0.72 mmol) in dry THF (20 mL) was added and stirred
for 6 h. Finally, the solvent was removed and the brown solid
was purified by silica gel column chromatography (3:1 hexane/
dichloromethane) giving biphenyl 7 as a white solid, mp 191–193 ꢀC
(167 mg, 95%).
IR (KBr): 3345 (O–H), 2983, 2228 (C^C), 1587, 1556 (C]C), 1165,
949, 866 (1,3,5-trisubst.). 1H NMR (CDCl3): 7.45 (d, 4H, J¼1.21 Hz,
H-2, H-6, H-20, H-60), 7.36 (t, 2H, J¼1.21 Hz, J¼1.21 Hz, H-4, H-40),
2.64 (s, 4H, OH), 1.58 (s, 24H, Me). 13C NMR (CDCl3): 133.9 (C-4, C-
40), 133.2 (C-2, C-6, C-20, C-60), 132.9 (C-1, C-10), 124.6 (C-3, C5, C-30,
C-50), 95.6 (^C–C–OH), 79.9 (^C–Ph), 65.5 (C–OH), 31.2 (Me).
Anal. Calcd for C32H34O4 (482.62): C, 79.64; H, 7.10. Found: C, 79.74;
H, 5.18.
IR (KBr): 3062 (ArC–H), 2975 (C–H), 2236 (C^C), 1654 (C]C),
1445 (CH3), 1352 (C–N), 820 (p-subst.), 810 and 698 (1,3,5-
trisubst.), 664 (C–Br). 1H NMR (CDCl3): 7.53 (t, 3H, J¼1.21 Hz, H-2,
H-4, H-6), 7.39 (d, 4H, J¼8.9 Hz, H-20, H-60), 6.66 (d, 4H, J¼8.9 Hz,
13
H-30, H-50), 3.00 (s, 12H, 2N–Me2). C NMR (CDCl3): 150.3 (C-40),
132.9 (C-1), 132.6 (C-30, C-50), 132.4 (C-20, C-60), 126.1 (C-2, C-6),
121.70 (C-3, C-5), 111.8 (C-4), 109.2 (C-10), 92.4 (C^C–Ph–Br),
85.59 (Me2N–Ph–C^C–), 40.2 (N–Me2). Anal. Calcd for C26H73N2Br
(447.37): C, 69.81; H, 5.18; N, 7.15. Found: C, 69.44; H, 5.12;
N, 7.08.
4.2.4. 3,30,5,50-Tetra(p-N,N-dimethylaminophenylethynyl)-
biphenyl (5)
4.4.2. 3,305,50-Tetra(ethynyl)biphenyl (8)
A
solution of 3,5,30,50-tetra(3-methyl-1-butyn-3-ol)biphenyl
A
solution of Ni[(PPh3)2]Cl2 (92.12 mg, 0.14 mmol), Bu4NI
(150 mg, 0.31 mmol) in dry toluene was treated with a catalytic
amount of anhydrous powder of NaOH and warmed at reflux
temperature for 5 h. After the solvent was removed giving 8 as
a solid, it was crystallised in hexane as a yellow solid, mp
189–191 ꢀC, in excellent yield (75 mg, 98%).
IR (KBr): 3055 (C^H), 1422, 1266, 896, 741 and 706 (1,3,5-tri-
subst.). 1H NMR (CDCl3): 7.60 (d, 4H, J¼1.2 Hz, H-5), 7.52 (t, 2H,
J¼1.2, 1.2 Hz), 3.13 (s, 4H). 13C NMR (CDCl3): 135.1 (C-1), 134.2 (C-6),
132.3 (C-5), 121.8 (C-4), 81.1 (C-3), 79.3 (C-2). Anal. Calcd for C20H10
(250.3): C, 95.97; H, 4.03. Found: C, 95.77; H, 3.88.
(51.7 mg, 0.14 mmol), powder of Zn (14 mg, 0.21 mmol) in dry THF
was stirred for 30 min and then was added 3 (60 mg, 0.14 mmol)
and stirred for 12 h at room temperature. Solvent was removed and
the residual brown oil was purified by silica gel column chroma-
tography giving 5 (66 mg, 65%) as a yellow oil.
IR (KBr): 3012 (ArC–H), 2988 (C–H), 2210 (C^C), 1670 (C]C,
conj.), 1486 (CH3), 1342 (C–N), 730 (Ph-subst.). 1H NMR (CDCl3):
7.90 (t, 2H, J¼7.5 Hz, H-4, H-40), 7.67 (d, 8H, J¼7.0 Hz, H-200, H-600),
7.62 (d, 8H, J¼7.00 Hz, H-300, H-500), 7.53 (dd, 4H, J¼7.5, 1.6 Hz, H-2,
H-6, H-20, H-60), 2.97 (s, 24H, 8NMe2). 13C NMR (CDCl3): 144.3
(C-400), 135.9 (C-1, C10), 134.7 (C-4, C-40), 133.8 (C-200, C-600), 122.08
(C-300, C-500), 111.70 (C-300, C-500), 111.03 (C-100), 97.64 (^C–BiPh),
85.45 (–C^C–Ph–NMe2), 42.16 (N–Me2). Anal. Calcd for C52H46N4
(726.97): C, 85.91; H, 6.38; N, 7.71. Found: C, 85.57; H, 6.18;
N, 7.54.
4.5. Synthesis of 3,5,30,50-tetra(p-N,N-dimethylamino)
(phenylethynyl)biphenyl (5) from 3,5,30,50-tetra
(ethynyl)biphenyl (5)
A mixture of p-(N,N-dimethylamino)-iodobenzene (494 mg,
2.0 mmol), dichloro bis(triphenylphosphine) palladium (31 mg,
0.04 mmol), cuprous iodide (0.01 mmol) and a solution of 3,5,30,50-
tetra(ethynyl)biphenyl (100 mg, 0.44 mmol) in triethylamine was
stirred at 40 ꢀC for 8 h, and then hydrolysed with a saturated
aqueous solution of ammonium chloride (30 ml) and a little
amount of potassium cyanide (10 mg) and extracted with
dichloromethane (20 ml). After solvent was removed, the residual
oil was purified by chromatography on silica gel column (10:1,
hexane/dichloromethane) giving the biphenyl 5 as a yellow oil
(281.5 mg, 88%).
4.3. Synthesis of 3,30,5,50-tetra(p-methoxy)(phenylethynyl)-
biphenyl (6)
4.3.1. 1-Bromo-3,5-di(p-methoxyethynyl)benzene (4)
To a mixture of 2 (38.33 mg, 0.20 mmol), dichloro bis(triphen-
ylphospine) palladium (15 mg, 0.061 mmol, 5 mol %) and cuprous
iodide (2 mol %) was added a solution of p-methoxy-iodobenzene
(57.48 mg, 0.30 mmol) in freshly distilled triethylamine and stirred
at 60 ꢀC for 24 h. The mixture was treated with a saturated aqueous
solution of ammonium chloride (20 ml) and a little amount of
potassium cyanide (5 mg) and extracted with dichloromethane
1H NMR (CDCl3): 7.67 (d, 8H, J¼6.99 Hz, H-11, H-4), 7.62 (d, 8H,
J¼6.99 Hz, H-3), 7.53 (dd, 4H, J¼7.53, 1.6 Hz, H-9), 7.9 (t, 2H,

J.G. Rodr´ıguez, T. Laparra / Tetrahedron 65 (2009) 2551–2555
2555
J¼7.53 Hz, H-11), 2.97 (s, 24H, H-1). 13C NMR (CDCl3): 144.3 (C-2),
Acknowledgements
135.9 (C-10), 134.7 (C-11), 133.8 (C-4), 122.08 (C-8), 111.70 (C-3),
111.03 (C-5), 97.64 (C-7), 85.45 (C-6), 42.16 (N–Me2). IR (KBr):
3012 (ArC–H), 2988 (C–H), 2210 (C^C), 1670 (C]C), 1486
(CH3), 1342 (C–N), 730 (1,3,5-trisubst.). Anal. Calcd for C52H46N4
(726.97): C, 85.91; H, 6.38; N, 7.71. Found: C, 85.66; H, 6.25;
N, 7.43.
We are grateful to the CAM and MEC of Spain, projects no.
S-0505/PPQ/0344 and CTQ-2006-15692-C02-01, respectively, for
financial support.
References and notes
4.6. Synthesis of 3,5,30,50-tetra(p-methoxyphenylethynyl)-
1. (a) Sainsbury, M. Tetrahedron 1980, 36, 3327; (b) Bringmann, G.; Walter, R.;
Weirich, R. Angew. Chem., Int. Ed. Engl.1990, 29, 977; (c) Bringmann, G.; Ewers, C. L.
J.; Walter, R. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 6, p 733; (d) Hassan, J.; Sevignon, M.; Gozzi, C.;
Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359.
2. (a) An-Hui, W.; Chun-Kit, H.; Henry, W. Adv. Synth. Catal. 2007, 349, 601; (b)
Yong, Z.; Hua-Hong, S.; Yong, C. Chin. J. Chem. 2006, 24, 1631.
3. (a) Tsuji, J. Palladium Reagents and Catalysts; Wiley: Chichester, UK, 1995;
Chapter 4, Section 1.1.4; (b) Farina, V. In Comprehensive Organometallic Chem-
istry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, 1995;
Vol. 12, Chapter 3.4.
biphenyl (6) from 3,5,30,50-tetra(ethynyl)biphenyl (6)
A mixture of p-iodoanisole (490 mg, 2.08 mmol), dichloro bis
(triphenylphosphine) palladium (31 mg, 0.04 mmol), cuprous io-
dide (0.01 mmol) and a solution of 3,5,30,50-tetra(ethynyl)biphenyl
(100 mg, 0.44 mmol) in triethylamine was stirred at 60 ꢀC (external
bath) for 12 h. After was hydrolysed with a saturated aqueous so-
lution of ammonium chloride (20 ml) and potassium cyanide
(5 mg), and extracted with dichloromethane (10 ml). After solvent
was removed, the residual oil was purified by silica gel column
chromatography (10:1, hexane/dichloromethane) giving the bi-
phenyl 6 as a yellow oil (398 mg, 83%).
´
´
4. (a) Rodrıguez, J. G.; Esquivias, J.; Lafuente, A.; Dıaz, C. J. Org. Chem. 2003, 68,
8120; (b) Rodriguez, J. G.; Esquivias, J.; Lafuente, A.; Rubio, L. Tetrahedron 2006,
62, 3112.
5. Semmelhack, M.; Helquist, P.; Jones, L. J. Am. Chem. Soc. 1971, 93, 5908.
6. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 1, 4467.
7. (a) Iyoda, M.; Otsuka, H.; Sato, K.; Nisato, N.; Oda, M. Bull. Chem. Soc. Jpn. 1990,
63, 80; (b) Rodrı´guez, J. G.; Tejedor, J. L.; Rumbero, A.; Canoira, L. Tetrahedron
2006, 62, 3075; (c) Semmelhack, M.; Helquist, P.; Jones, L.; Keller, L.; Meldelson,
L.; Pinano, L.; Smith, J.; Stauffer, R. J. Am. Chem. Soc. 1981, 103, 6460.
8. Rodrı´guez, J. G.; Canoira, L.; Benito, Y. Appl. Organomet. Chem. 1987, 1, 535;
Rodrı´guez, J. G.; Canoira, L. J. Heterocycl. Chem. 1985, 22, 883; Rodrı´guez, J. G.;
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IR (KBr): 2976 (C–H), 2862 (O–Me), 2360 and 2340 (C^C),
1535, 1267 (ArC–O–Me), 841 (1,3,5-trisubst.). 1H NMR (CDCl3):
7.58 (d, 4H, J¼1.2 Hz, H-2, H-6, H-20, H-60), 7.46 (d, 8H, J¼8.9 Hz,
H-200, H-600), 7.31 (t, 2H, J¼1.2 Hz, H-4, H-40), 6.89 (d, 8H, J¼8.9 Hz,
13
H-300, H-500), 3.83 (s, 12H, Me). C NMR (CDCl3): 160.0 (C-400),
133.3 (C-4, C-40), 133.3 (C-2, C-6, C-20, C-60), 132.75 (C-1, C-10),
125.6 (C-2, C-6, C-20, C-60), 123.4 (C-3, C-5, C-30, C-50), 114.1 (C-300,
C-500), 114.0 (C-100), 91.2 (^C–BiPh), 86.0 (^C–Ph–OMe), 55.3
(Me). Anal. Calcd for C48H34O4 (674.79): C, 85.44; H, 5.08. Found:
C, 85.13; H, 5.22.