Microwave-promoted palladium catalysed Suzuki cross-coupling reactions of benzyl halides with arylboronic acid

Article abstract of DOI:10.3184/174751913X13687900303985

Simple catalytic systems for the coupling of benzyl halides with phenylboronic acid under microwave conditions were tested. Microwave-promoted Suzuki reaction of arylboronic acid with benzyl halides catalysed by PdCl2(PPh3)2 in the mixed solvents DMF/H2O is reported to give diaryl methane derivatives in good to high yield.

Full text of DOI:10.3184/174751913X13687900303985

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 375
JUNE, 375–376
Microwave-promoted palladium catalysed Suzuki cross-coupling
reactions of benzyl halides with arylboronic acid
Yu-Quan Zhang*
College of Chemistry and Chemical Engineering, Longdong University, Xifeng, Gansu 745000, P. R. China
Simple catalytic systems for the coupling of benzyl halides with phenylboronic acid under microwave conditions
were tested. Microwave-promoted Suzuki reaction of arylboronic acid with benzyl halides catalysed by PdCl2(PPh3)2
in the mixed solvents DMF/H2O is reported to give diaryl methane derivatives in good to high yield.
Keywards: Suzuki cross-coupling reactions, benzyl halides, diaryl methanes, microwave irradiation microwave
The palladium catalysed Suzuki–Miyaura cross-coupling reac-
tion1 between arylboronic acids and aryl halides or triflates has
proved to be a very popular and versatile method for forming
the carbon–carbon single bonds of biaryls.2,3 Diaryl methane
derivatives are important building blocks in organic synthesis
because of their industrial applications. Organoboron reagents
exhibit greater functional group compatible with organo zinc
or Grignard reagents. Moreover, the innocuous nature of
boronic acids, which are generally nontoxic and thermally air
and moisture-stable, is a practical advantage of the Suzuki
reaction relative to other coupling processes. Negishi and
co-workers had earlier reported Pd(0)-and Ni(0)-catalysed
syntheses of unsym- metrical diarylmethanes via the corre-
sponding benzylzinc bromides or benzylmagnesium chlorides
with aryl bromides or iodides.4 There are other instances in
which Pd(0)-catalysed couplings of benzylic halides under
Stille-type conditions have been reported.5 Other Suzuki
coupling reactions of benzyl halides have been described.6–15
Several non-traditional methods have been developed for
the Suzuki–Miyaura synthesis of unsymmetrical biaryls such
as high intensity ultrasound16–17 and especially microwave irra-
diation,18–22 which also promotes the reaction of aryl chlorides
and acid chlorides.
The main goal of our work was to see if the Suzuki–Miyaura
coupling of arylboronic acids with benzylic halides can be
promoted by microwave irradiation. The second aim was also
to find out if this reaction can also be used for the preparation
of unusually substituted diarylmethane derivatives, as shown
in Scheme 1.
The microwave-assisted crossing-coupling reaction of
phenylboronic acid with 2-bromomethyl naphthalene, afford-
ing 2-naphthyl phenyl methane, was chosen as a model reac-
tion. The effect of catalysts, base, reaction time, and mole
ratios, were examined.
obtained (90%). It is important to note that when the amount of
catalyst is increased from entry 2 to 5 or 7 mmol%, the yield of
the product did not improve using K2CO3 as base even after
irradiation the reaction mixture for 15min (Table 1, entries 11
and 12).
We investigated the different mole ratios on microwave–
assisted crossing-coupling reaction of phenylboronic acid with
2-bromomethylnaphthalene, the results show the best mole
ratio is phenylboronic acid: 2-bromomethylnaphthalene:
K2CO3: [PdCl2(PPh3)2] = 1:1.2:2.5:0.05.
Applying the optimised conditions, we synthesised the 3a–j
under microwave irradiation. The results are listed in Table 2.
Note that benzyl bromides underwent smooth coupling with
phenylboronic acid, whereas other halogens present on the
aromatic ring remained unaffected (Table 2, entries 3b and
3h). However, aromatic bromides underwent the Suzuki
cross-coupling reaction selectively (Table 2, entry 3d) under
microwave irradiation. Without microwave irradiation 3d was
not obtained.
Experimental
CAUTION: The palladium catalyst must be well distributed in the
reaction mixture and the reaction equipment must not be closed.
Microwave irradiation was carried out with a commercial domestic
microwave oven Glanzwp 750B at 2450Hz. Melting points were
determined with an electric-melting point apparatus and are uncor-
rected. IR spectra were recorded in KBr on an Alpha Centauri FT-IR
spectrophotometer and 1H NMR spectra were recorded on a BRUKER
PT 200MHz or 400 MHz instrument using CDCl3 as solvent and TMS
as internal reference. Mass spectra were recorded on a QP-1000A GC-
MS using the electron impact mode (70ev) or Bruker Daltonics APEX
II 47eFT-ICR. All solvents were used without further purification.
Table
1
Effect of catalyst on Suzuki cross-coupling of
The catalytic study (Table 1) showed that in the absence of
catalyst, there was no reaction even after microwave irradia-
tion of 30min (Table 1, entry 9). On the other hand Pd (PPh3)2Cl2
and K2CO3 were found to be the best catalyst system and the
crossed coupled product was isolated in 90% yield (Table 1,
entries 5 and 6), moderate yields (60% and 84%) of the 2-
naphthylphenylmethane were obtained in the presence of 2
and 5mol% of PdCl2(PPh3)2 as catalyst using different base
(Table 1, entries 1–4). However, using 5mol% of PdCl2(PPh3)2
and K2CO3 the reaction was complete in a short time (13 min)
and an excellent yield of 2-naphthylphenylmethane was
2-bromomethyl naphthalene with phenylboronic acid in DMF/
H2O under microwave irradiationa
Entry
Catalyst/mmol%
Pd (PPh3)2Cl2
Base
Time/min Yields /%b
1
2
5
5
5
5
5
7
3
2
0
5
5
5
NaOH
KF/Al2O3
KF
13
13
13
13
13
13
13
13
30
11
15
20
60
80
3
84
4
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
70
5
90
6
90(86c)
82
7
8
70
9
—
10
11
12
78
90
90
a Conditions: 2-bromomethyl naphthalene (1.2 mmol), phenyl-
boronic acid (1 mmol), base (2.5 mmol), 675W.
b Yield of isolated product.
Scheme 1
c Reaction temperature 130 °C, reaction time 10 h, without
microwave irradiation.
* Corresponding author E-mail: zhyq118@sohu.com

376 JOURNAL OF CHEMICAL RESEARCH 2013
Table 2 fast palladium catalysed coupling reaction under
Financial support by the Natural Science Foundation of
China and Science Technology Development Foundation of
Longdong University is acknowledged.
microwave irradiationa
Product
ArCH2X
Yields (%)b
M.p. °C/Lit
3a
3a
3b
3c
3d
3e
3f
3g
3h
3i
C6H5CH2Br
C6H5CH2Cl
92
85
88
82
86
90
92
90
91
84
Oil23
Oil23
Received 4 March 2013; accepted 12 April 2013
Paper 1301818 doi: 10.3184/174751913X13687900303985
Published online: 12 June 2013
3-Cl-C6H4CH2Br
2-NO2-C6H4CH2Br
4-Br-C6H4CH2Br
4-NO2-C6H4CH2Br
4-BrCH2-C6H4CH2Br
2-C10H7CH2Br
Oil24
Oil25
84–85 (86–8726)
30(3127)
85–86(8626)
57–58(5828)
Oil23
References
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4-Cl-C6H4CH2Br
1-C10H7CH2Br
52–54
a Conditions: benzylhalide (1.2 mmol), phenylboronic acid
(1 mmol), K2CO3 (2.5 mmol), PdCl2(PPh3)2 (5% mmol), 13 min-
utes at 675 W.
4
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General procedure
Base K2CO3 (2.5 mmol, and PdCl2(PPh3)2 (0.05 mmol) catalyst were
added to the solution of phenylboronic acid (1 mmol) and benzyl
halide (1.2 mmol) in 12 mL solvent of N,N-diethyl formamide (DMF)
(10 mL) and H2O (2 mL). The reaction mixture was stirred and then
irradiated for 13 minutes at 675W under a nitrogen atmosphere. It was
cooled, the precipitate was filtrated and filtrate was poured into a satu-
rated aqueous sodium chloride solution (50 mL) and extracted with
diethyl ether (3×15 mL). The extract was then dried over magnesium
sulfate. The solution was concentrated to yield the crude product,
which was separated by column chromatography on silica gel (eluent:
petroleum/ethyl acetate = 10:1) and identified by spectroscopic
analyses.
3i: M.p. 52–54 °C. IR: ν = 3058, 3023, 2906, 2852, 1595, 1490,
1449, 1394, 1160, 791, 772, 734, 703 cm−1. 1H NMR (200MHz,
CDCl3): δH = 7.45–7.20 (m, 9H), 7.73 (d, J = 7.8 Hz, 1H), 7.83–8.04
(m, 2H), 4.48 (s, 2H). HRMS calcd C17H14: 218.1095, found:
218.1088.

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