Palladium-doped mixed oxides as 'slow-release' catalysts for suzuki couplings

Article abstract of DOI:10.1055/s-2007-986639

Palladium-containing sol-gel materials are efficient catalysts for Suzuki couplings. Especially good results are obtained under microwave irradiation in water. At least in this solvent, homogeneous palladium species are responsible for the catalytic activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-986639

LETTER
2579
Palladium-Doped Mixed Oxides as ‘Slow-Release’ Catalysts for Suzuki
Couplings
P
alladium-Doped M
l
ixed O
i
xides as ‘Slo
K
w
Release’ Cataly
a
sts for Suz
z
uki Coupli
m
a
b
c
Institut für Organische Chemie, Universität des Saarlandes, 66123 Saarbrücken, Germany
Lehrstuhl für Technische Chemie, Universität des Saarlandes, 66123 Saarbrücken, Germany
Institut für Anorganische und Analytische Chemie und Radiochemie, Universität des Saarlandes, 66123 Saarbrücken, Germany
Fax +49(681)3022409; E-mail: u.kazmaier@mx.uni-saarland.de
Received 28 June 2007
formation was given, with the true catalyst possibly being
Pd0 nanoclusters or molecular, ‘naked’ Pd species.
Abstract: Palladium-containing sol-gel materials are efficient
catalysts for Suzuki couplings. Especially good results are obtained
under microwave irradiation in water. At least in this solvent,
homogeneous palladium species are responsible for the catalytic
activity.
Since perovskites are difficult to prepare and nothing is
known about the importance of their special crystalline
structure for the observed catalytic activity in Suzuki cou-
plings, we decided to test mixed oxide materials of identi-
cal composition. Based on our extensive experience with
sol-gel materials as reliable and reproducible heteroge-
neous catalysts a suitable sol-gel process was selected.13,14
The sol-gel process is a mild synthetic procedure for metal
oxides from hydrolysable precursors. If carried out cor-
rectly, it can be also used for the preparation of porous
mixed oxides, where the formation of single-phase oxides
is suppressed.13 The latter is of crucial importance for cat-
alytic properties, since mixtures of single-phase oxides do
not exhibit new catalytic properties. The sol-gel process
applied tolerates the precursors of the different metal ions
used for the preparation of the materials shown in
Figure 1.15 In addition to rather simple synthesis condi-
tions, the sol-gel procedure also allows to add, substitute
and remove elements without changing the basic prepara-
tion procedure, thus allowing to screen a broad variety of
materials in a combinatorial way for potential catalytic
activity.16 From 50 compositions studied in the primary
screening approach, only the five most active ones
(Figure 1, A, B, C, F, G) and two Pd-free materials (D and
E) were selected as reference for more detailed studies.
Key words: cross-couplings, boronic acids, microwave irradiation,
sol-gel catalysts, Suzuki couplings
The Suzuki coupling is one of the most popular cross-cou-
pling reactions, as illustrated by a wide range of synthetic
applications.1 The special charm of the Suzuki reaction
lies in its high reliability, broad functional group toler-
ance, as well as low toxicity associated with the boron
compounds. The reaction is traditionally performed in or-
ganic solvents using a homogeneous Pd catalyst in the
presence of phosphine ligands and a base.1 The removal of
the residual palladium and the ligands from the product is
not a trivial issue, and therefore heterogeneous catalysts
have become more and more popular. The heterogeneous
catalysts not only simplify the separation of the catalyst,
but also allow a reuse of the removed material, thus reduc-
ing process costs. Therefore, over the past few years,
numerous supported Pd catalysts have been reported in
the literature, e.g. Pd/C,2 Pd/zeolite,3 Pd/sepiolite,4 Pd/
layered double hydroxide (LDH),5 as well as Pd on
several metal oxides.6 Although the catalyst is applied in
the ‘heterogeneous’ form, desorption of the transition
metal from the support can occur, resulting in its entry
into a conventional solution-phase catalytic cycle.7 This
has initiated investigations into the nature of the catalyti-
cally active species.8 Recently, Ley et al. reported on the
application of palladium-containing perovskites (e.g.
La1Fe0,57Cu0,38Pd0,05Ox
A
Fe0,57Cu0,38Pd0,05Ox
B
La1Fe0,95Pd0,05Ox
C
Fe1Ox
D
La1Fe0,95Ni0,05Ox
Fe0,95Pd0,05Ox
F
La1Pd0,05Ox
G
E
La1Fe0.57Cu0.38Pd0.05Ox),9 a heterogeneous catalyst origi- Figure 1 Sol-gel catalysts used for Suzuki couplings
nally developed for automotive emission control.10 Small
levels of Pd leaching were found to occur during reaction
(ca. 2 ppm in solution) and application of a three-phase
As a model reaction we investigated the Suzuki coupling
of p-benzyloxyphenylboronic acid (1) and bromoanisole
2 in the presence of several heterogeneous catalysts. As
test proved that at least a part of the reactivity was associ-
ated with these leached species.11 Leaching was caused by
solvent, we used a two-phase system (EtOH–toluene) and
addition of aryl halides to the catalyst, also observed in
aqueous K2CO3 as a base. In principle, Pd/C could also be
other systems.12 A plausible mechanism for catalyst
used as a catalyst (Table 1, entry 1), which is in good
agreement with the work of Köhler et al.2b Pd/C obviously
is more suitable than Pd/BaSO4. Even after refluxing for
SYNLETT 2007, No. 16, pp 2579–2583
0
1
.1
0
.2
0
0
7
two days in the presence of the latter catalyst only a 50%
yield was obtained (entry 2).
Advanced online publication: 28.08.2007
DOI: 10.1055/s-2007-986639; Art ID: G20607ST
© Georg Thieme Verlag Stuttgart · New York

2580
U. Kazmaier et al.
LETTER
Table 1 Suzuki Couplings with Various Heterogeneous Catalysts
more reactive than the others (A, B) and therefore we used
C as the standard catalyst for further Suzuki couplings.
OMe
As already mentioned, microwave irradiation can signifi-
cantly improve the reaction, especially if the coupling re-
action is carried out in water.20 Therefore, we investigated
the coupling of various aryl halides 4 with phenylboronic
acid (5) in aqueous solution (Table 2). The mixture was
heated in a microwave (MW) oven to 150 °C (constant
temperature).21 For comparison, the reaction with iodo-
benzene (4a) was also carried out in EtOH–toluene. Inter-
estingly, almost no reaction was observed in EtOH–
toluene after 30 minutes (entry 1), whereas the coupling
product 6 was obtained in 50% yield in water (entry 2).
Prolonging the reaction time to one hour increased the
yield to 84% (entry 3). Longer reaction times or doubling
the amount of catalyst gave no further improvement
(entries 4 and 5). As expected the reactivity of the aryl
halides decreased in the order I >Br >>Cl ≈ OTf. With
bromobenzene (4b) the yield was a little worse (entry 6),
compared to the iodo derivative, but only traces of the
coupling product were obtained with chlorobenzene (4c)
or phenyltriflate (4d) (entries 7 and 8).
B(OH)2
Br
catalyst
+
EtOH–toluene
2 M K2CO3, ∆
OBn
OMe
1
2
OBn
3
Entry Catalyst
Cat.
(%)a
Pd
Reaction
conditions
Yield
(%)
(%)a
1
2
3
Pd/C
2.8
2.8
2.8
20 h
44 h
59b
46b
Pd/BaSO4
Pd/BaSO4
Microwave, 100 W, 16b
30 min, 150 °C
4
5
6
7
8
A
B
C
D
E
1.2
2.7
1.2
3.0
1.2
0.06
0.14
0.06
0
24 h
24 h
24 h
24 h
24 h
100c
100c
100c
0
Table 2 Suzuki Couplings in Water
0
traces
X
B(OH)2
a Amount in mol%.
b Isolated yield.
La1Fe0,95Pd0,05Ox
+
c Yield was determined by GC.
2 M K2CO3, MW, 150 °C
6
4
5
Transition-metal-catalyzed couplings belong to the best-
investigated reactions carried out under microwave irradi-
ation,17 and there were several reports in the literature,
especially on Suzuki couplings. Unfortunately with Pd/
BaSO4 no improvement could be observed (entry 3).
Therefore, we next investigated the sol-gel catalysts
shown in Figure 1. The surface area of the sol-gel-derived
mixed oxides (25 m2/g BET-surface area, and a pore size
of 3 nm with a surprisingly narrow pores size distribution
was measured for La1Fe0,95Pd0,05Ox) may be responsible
for the unusual activity of these new materials. A 3-mg
amount of the corresponding catalyst (A–E) was used for
1 mmol of bromoanisole and the reaction was monitored
by GC–MS.18 Tetradecane was added as internal standard
to determine the conversion rate. Interestingly, all cata-
lysts containing Pd (entries 4–6) showed complete con-
version after 24 hours, indicating that the composition of
the mixed oxide played only a minor role. The results also
document, that the crystalline nature of the perovskites is
not required to obtain catalytic activity.
Entry Halide
X
Solvent
Cat.
(%)a
Time
Yield
(min) (%)b
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4a
4b
4c
4d
I
EtOH–toluene 1.2
30
30
60
90
60
60
60
60
traces
50
I
H2O
H2O
H2O
H2O
H2O
H2O
H2O
1.2
1.2
1.2
2.4
1.2
1.2
1.2
I
84
I
87
I
86
Br
Cl
OTf
74
traces
traces
a Amount in mol%.
b Isolated yields.
We used these optimized reaction conditions for the
coupling of several electron-rich as well as electron-poor
aromatic halides 7 (Table 3).
No big difference in activity was found if one of the ele-
ments was removed, as long as Pd was part of the catalyst.
Absolutely no reaction was observed with the palladium-
free catalyst D (entry 7). Replacing the palladium by
nickel (E) resulted in traces of coupling product (entry 8).
This is not surprising, because nickel can also act as
catalyst in coupling reactions.19 A direct comparison of
the different catalysts showed that catalyst C was slightly
In general, the yields were high, except in the case of the
heterocyclic derivative 8h. The major side product found
in this reaction was biphenyl 6 resulting from a homo-
coupling of the phenylboronic acid (5).22
The drastic increase in the reactivity by switching from
the two-phase system (EtOH–toluene) to water raised the
question about the catalytically active species. Is the
Synlett 2007, No. 16, 2579–2583 © Thieme Stuttgart · New York

LETTER
Palladium-Doped Mixed Oxides as ‘Slow-Release’ Catalysts for Suzuki Couplings
2581
col with the used catalyst to find out if repeated use affects
the catalytic activity. The residue of the first centrifuga-
tion/filtration was subjected to microwave irradiation for
a second and a third time, but the catalytic activity of the
filtered solution remained high (Table 4, entry 3 and 4).
The heterogeneous catalyst apparently leaches repeatedly
comparable amounts of Pd and thus acts as a ‘controlled
release’ material for highly active Pd. If solubilized palla-
dium species are responsible for the catalytic activity, the
composition of the ‘heterogeneous catalyst’ should not
play any role. Under the two-phase conditions (EtOH–tol-
uene) we observed some differences in the catalytic activ-
ity, but these differences could be minimized if the
reaction was carried out in water. Therefore we also inves-
tigated the coupling of 5 and 7i in the presence of other
catalysts such as La1Pd0.05Ox (G) and Fe0.95Pd0.05Ox (F).
And indeed, both gave the same yields as catalyst C.
Table 3 Suzuki Couplings of Various Aryl Halides
1.2 mol% cat. C
PhB(OH)2
ArX
+
ArPh
2 M K2CO3, H2O
MW, 150 °C, 1 h
7
5
8
Entry Aryl halide
Product
Yield (%)a
82
Ph
I
1
O2N
O2N
8a
7a
OH
OH
I
Ph
2
94
7b
8b
I
Ph
3
74
72
Table 4 Comparison of Heterogeneous and Homogeneous
Catalysis
HO
HO
8c
7c
B(OH)2
Br
+
CHO
Br
Ph
1.2 mol% catalyst
4
2 M K2CO3, H2O
MW, 150 °C, 1 h
OHC
EtOOC
HOOC
7d
8d
8i
7i
5
Ph
Br
Entry Catalyst Reaction Conditions
Yield
(%)b
5
96
89
78
56
H2N
H2N
1
2
C
C
Irradiation with heterogeneous catalyst
93
8e
7e
1st run: homogeneous solution after irradiation 90
(60 min) and filtration
OHC
OHC
Ph
Ph
Br
6
3
4
C
C
2nd run: homogeneous solution after irradiation 88
(60 min) and filtrationa
7f
8f
Br
3rd run: homogeneous solution after irradiation 94
(60 min) and filtrationa
7
MeO
MeO
7g
8g
5
6
F
Irradiation with heterogeneous catalyst
93
Br
Ph
N
N
G
Irradiation with heterogeneous catalyst
93
8
N
N
a The heterogeneous filtered catalyst from the last run was irradiated
again for 60 min without the substrate.
b Isolated yields.
7h
8h
a Isolated yields.
The repeated leaching activity of the used catalyst raises
the question, how much solubilized Pd is actually required
for the observed activity. Therefore, we analyzed a freshly
irradiated and filtered solution of catalyst C by ICP–MS.23
Besides 2.9 ppm of lanthanum we found 0.336 ppm of
palladium in solution, which is equivalent to 0.0016 mol%
Pd, correlating with a turnover number (TON) of 62500
and a dissolution of 5.2% of the original Pd-content of the
mixed oxide. Such a high TON not only confirms an ex-
tremely high catalytic activity, it also indicates, that the
mixed oxides with a low Pd-content used here might be
good for up to 20 subsequent reactions.24
heterogeneous catalyst per se responsible for the activity,
or are catalytically active palladium species, such as col-
loids, going into solution, as reported for similar sys-
tems?2c In order to answer this question, catalyst C was
subjected to the reaction conditions used (2 M K2CO3,
H2O, MW, 150 °C) without the substrates. After one hour
the catalyst was removed by centrifugation and subse-
quent filtration. Phenylboronic acid (5) and p-bromobenz-
aldehyde (7i) were added to the clear solution, and the
resulting mixture was again irradiated for one hour. And
indeed, the yield of coupling product (Table 4, entry 2)
was nearly identical to the result obtained in the presence
of the catalyst (entry 1). We repeated the leaching proto-
Synlett 2007, No. 16, 2579–2583 © Thieme Stuttgart · New York

2582
U. Kazmaier et al.
LETTER
(12) Lipshutz, B. H.; Tasler, S.; Chrisman, W.; Spliethoff, B.;
Tesche, B. J. Org. Chem. 2003, 68, 1177.
(13) Frenzer, G.; Maier, W. F. Annu. Rev. Mater. Res. 2006, 36,
281.
(14) Kim, D. K.; Maier, W. F. J. Catal. 2006, 238, 142.
(15) Preparation of Catalysts: The catalysts were prepared by a
modified sol-gel method. The following precursors,
Cu(NO3)2·3H2O, Fe(NO3)3·9H2O, La(NO3)3·6H2O,
Ni(NO3)2·6H2O, and Pd(NO3)2·H2O, were dissolved in
distilled H2O and mixed with ethylene glycol and nitric acid.
The molar ratio was M/H2O/ethylene glycol/HNO3 =
1:40:20:4 (M as the sum of metal ions). The solutions were
dried and calcined in air for 12 h at 80 °C, for 60 h at 105 °C
and for 5 h at 400 °C with a heating rate of 6 °C/ h each. After
calcination the powders were ground and sieved.
(16) Maier, W. F.; Stöwe, K.; Sieg, S. Angew. Chem. Int. Ed.
2007, 46, 6016.
In conclusion we could show that palladium-containing
sol-gel materials are efficient catalysts for Suzuki cou-
plings in water. At least in this solvent, homogeneous
palladium species are responsible for the catalytic acti-
vity. The mixed oxides could be used repeatedly to release
very small amounts of Pd into solution, which very effec-
tively catalyzed the reaction of interest. This raises the
possibility of using the mixed oxides for controlled Pd-re-
lease, which is the subject of additional studies.
Acknowledgment
Financial support by the Deutsche Forschungsgemeinschaft as well
as the Fonds der Chemischen Industrie is gratefully acknowledged.
(17) (a) Kappe, C. O. Angew. Chem. Int. Ed. 2004, 43, 6250.
(b) Arvela, R. K.; Leadbeater, L. E. Org. Lett. 2005, 7, 2101.
(18) General Procedure for Suzuki Couplings in EtOH–
Toluene: To a two-phase system of toluene (4 mL), EtOH
(1.3 mL) and 2 M K2CO3 (2 mL), aryl halide (1.0 mmol),
boronic acid (1.1 mmol) and catalyst (for mol% of Pd see
Table 1) were added and the mixture was heated to reflux for
the specified time. After cooling to r.t., H2O was added and
the aqueous layer was extracted with Et2O (3 ×). After
drying (Na2SO4) and evaporation of the solvent, the crude
product was purified by column chromatography (silica gel,
hexanes–EtOAc).
4-Benzyloxy-4¢-methoxybiphenyl (3): According to this
general procedure 3 was obtained from 4-bromoanisole (187
mg) and 4-benzyloxyphenylboronic acid (251 mg) as a white
solid; mp 170 °C. 1H NMR (500 Hz, CDCl3): d = 7.45 (m, 6
H), 7.40 (dd, J = 7.3, 7.7 Hz, 2 H), 7.34 (t, J = 7.3 Hz, 1 H),
7.04 (d, J = 8.7 Hz, 2 H), 6.96 (d, J = 8.7 Hz, 2 H), 5.11 (s,
2 H), 3.85 (s, 3 H). 13C NMR (500 Hz, CDCl3): d = 158.7,
157.9, 137.0, 133.7, 133.4, 128.6, 128.0, 127.7, 127.5,
115.1, 114.2, 70.1, 55.3. Anal. Calcd for C20H18O2 (290.36):
C, 82.73; H, 6.25. Found: C, 82.99; H, 6.45. HRMS: m/z
[M+] calcd for C20H18O2: 290.1307; found: 290.1340.
(19) Shirakawa, E.; Yamasaki, K.; Hiyama, T. Synthesis 1998,
1544.
References and Notes
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M. Chem. Rev. 2002, 102, 1359. (c) Miyaura, N. Top. Curr.
Chem. 2002, 11. (d) Miyaura, N. In Metal-Catalyzed Cross-
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(2) (a) Sakurai, H.; Tsukuda, T.; Hirao, T. J. Org. Chem. 2002,
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(21) General Procedure for Suzuki-Couplings in Water
under Microwave Irradiation: In a glass tube were placed
aryl halide (1 mmol), phenylboronic acid (183 mg, 1.5
mmol), catalyst (1.2 mol%), 2 M K2CO3 (2 mL) and H2O (4
mL). The sealed vessel was placed into the microwave. The
mixture was irradiated in a sealed tube at 150 °C (initial
power 100 W). After 60 min the reaction was cooled to r.t.
Then H2O was added and the aqueous layer was extracted
with Et2O (3 ×). After drying (Na2SO4) and evaporation of
the solvent, the crude product was purified by column
chromatography (silica gel, hexanes–EtOAc).
4-Nitrobiphenyl (8a): yellow solid; mp 112 °C. 1H NMR
(500 Hz, CDCl3): d = 8.30 (d, J = 8.9 Hz, 2 H), 7.74 (d, J =
8.9 Hz, 2 H), 7.63 (d, J = 7.1 Hz, 2 H), 7.50 (dd, J = 7.1, 7.5
Hz, 2 H), 7.45 (t, J = 7.5 Hz, 1 H). 13C NMR (500 Hz,
CDCl3): d = 147.6, 147.1, 138.7, 129.1, 128.9, 127.8, 127.4,
124.1.
2-Hydroxybiphenyl (8b): white solid; mp 57 °C. 1H NMR
(500 Hz, CDCl3): d = 7.52–7.55 (m, 4 H), 7.44 (m, 1 H),
7.28–7.33 (m, 2 H), 7.03–7.06 (m, 2 H), 5.32 (br s, 1 H). 13
NMR (500 Hz, CDCl3): d = 152.4, 137.1, 130.2, 129.2,
129.1, 129.1, 128.1, 127.8, 120.8, 115.8.
C
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LETTER
Palladium-Doped Mixed Oxides as ‘Slow-Release’ Catalysts for Suzuki Couplings
2583
4-Hydroxybiphenyl (8c): white solid; mp 57 °C. 1H NMR
J = 7.2 Hz, 1 H). 13C NMR (500 Hz, CDCl3): d = 157.5,
154.9, 134.3, 134.3, 129.4, 129.0, 127.0.
(500 Hz, CDCl3): d = 7.55 (d, J = 7.5 Hz, 2 H), 7.49 (d, J =
8.6 Hz, 2 H), 7.42 (dd, J = 7.4, 7.5 Hz, 2 H), 7.31 (t, J = 7.4
Hz, 1 H), 6.91 (d, J = 8.6 Hz, 2 H), 4.81 (br s, 1 H).13C NMR
(500 Hz, CDCl3): d = 155.0, 140.7, 134.1, 128.7, 128.4,
126.7, 115.6.
Biphenyl-4-carbaldehyde (8i): white solid; mp 59 °C. 1H
NMR (500 Hz, CDCl3): d = 10.06 (s, 1 H), 7.95 (d, J = 8.3
Hz, 2 H), 7.75 (d, J = 8.3 Hz, 2 H), 7.64 (d, J = 7.1 Hz, 2 H),
7.50 (dd, J = 7.1, 7.5 Hz, 2 H), 7.42 (t, J = 7.5 Hz, 1 H). 13
NMR (500 Hz, CDCl3): d = 191.8, 147.1, 139.6, 135.1,
130.2, 128.9, 128.4, 127.6, 127.3.
C
Biphenyl-4-carboxylic Acid (8d): white solid; mp 215 °C.
1H NMR (500 Hz, DMSO-d6): d = 13.00 (br s, 1 H), 8.03 (d,
J = 8.4 Hz, 2 H), 7.79 (d, J = 8.4 Hz, 2 H), 7.73 (d, J = 7.4
Hz, 2 H), 7.50 (dd, J = 7.4, 7.6 Hz, 2 H), 7.42 (t, J = 7.6 Hz,
1 H), 3.87 (s, 3 H). 13C NMR (500 Hz, DMSO-d6): d = 167.1,
144.2, 138.9, 131.6, 129.9, 129.0, 128.2, 126.9, 126.7.
Biphenyl-4-ylamine (8e): orange-brown solid (162 mg,
0.96 mmol, 96%); mp 53 °C. 1H NMR (500 Hz, CDCl3): d =
7.57 (dd, J = 1.2, 8.2 Hz, 2 H), 7.45 (d, J = 8.4 Hz, 2 H), 7.41
(dd, J = 7.3, 8.2 Hz, 2 H), 7.30 (dt, J = 1.2, 7.3 Hz, 1 H), 6.77
(d, J = 8.4 Hz, 2 H), 3.73 (br s, 2 H). 13C NMR (500 Hz,
CDCl3): d = 145.8, 141.1, 131.5, 128.6, 128.0, 126.4, 126.2,
115.3.
(22) Moreno-Mañas, M.; Pérez, M.; Plaixats, R. J. Org. Chem.
1996, 61, 2346.
(23) Determination of Pd and La Concentrations in Solution
with ICP–MS: ICP–MS was conducted with a VG
Elemental Plasma Quad 3 instrument. The examined
isotopes were 105Pd and 139La. Calibration was carried out
with external standards of 10 ppt, 100 ppt, 1 ppb, 2 ppb, 5
ppb, 10 ppb and 100 ppb palladium and lanthanum. The
freshly irradiated (100 W, 150 °C, 1 h) and filtered solution
of catalyst C was diluted to 1:20, 1:30, 1:100 and 1:200. A
3% nitric acid solution was added to all samples. The
average of the Pd and La concentrations in solution was
calculated from these acquired concentrations.
(24) For some other reports about cross-couplings with
‘homeopathic’ amounts of Pd, see: (a) de Vries, A. H. M.;
Parlevliet, F. J.; Schmieder van de Vondervoort, L.;
Mommers, J. H. M.; Henderickx, H. J. W.; Walet, A. M.; de
Vries, J. G. Adv. Synth. Catal. 2002, 344, 996. (b) de Vries,
A. H. M.; Mulders, J. M. C. A.; Mommers, J. H. M.;
Henderickx, H. J. W.; de Vries, J. G. Org. Lett. 2003, 5,
3285. (c) Schmidt, A. F.; Smirnov, V. V. J. Mol. Catal. A:
Chem. 2003, 203, 75. (d) Alimardanov, A.; de Vondervoort,
L. S. V.; de Vries, A. H. M.; de Vries, J. G. Adv. Synth.
Catal. 2004, 346, 1812. (e) Arvela, R. K.; Leadbeater, N. E.;
Sangi, M. S.; Williams, V. A.; Granados, P.; Singer, R. D.
J. Org. Chem. 2005, 70, 161.
Biphenyl-3-carbaldehyde (8f): colorless liquid. 1H NMR
(500 Hz, CDCl3): d = 10.09 (s, 1 H), 8.11 (dd, J = 1.6, 1.6
Hz, 1 H), 7.86 (dd, J = 1.6, 7.7 Hz, 2 H), 7.63 (d, J = 7.7 Hz,
2 H), 7.61 (dd, J = 7.7, 7.7 Hz, 1 H), 7.48 (dd, J = 7.3, 7.7
Hz, 2 H), 7.41 (t, J = 7.3 Hz, 1 H). 13C NMR (500 Hz,
CDCl3): d = 192.2, 142.1, 139.6, 136.9, 133.0, 129.4, 128.9,
128.6, 128.1, 128.0, 127.1.
4-Methoxybiphenyl (8g): white solid; mp 88 °C. 1H NMR
(500 Hz, CDCl3): d = 7.54–7.58 (sh, 4 H), 7.48 (dd, J = 7.5,
7.9 Hz, 2 H), 7.32 (t, J = 7.5 Hz, 1 H), 7.00 (d, J = 8.8 Hz, 2
H), 3.87 (s, 3 H). 13C NMR (500 Hz, CDCl3): d = 159.1,
140.8, 133.8, 128.7, 128.1, 126.7, 126.6, 114.2, 55.3.
5-Phenylpyrimidine (8h): white solid; mp 41 °C. 1H NMR
(500 Hz, CDCl3): d = 9.21 (s, 1 H), 8.95 (s, 2 H), 7.58 (d,
J = 7.5 Hz, 2 H), 7.52 (dd, J = 7.2, 7.5 Hz, 2 H), 7.47 (t,
Synlett 2007, No. 16, 2579–2583 © Thieme Stuttgart · New York