Iron-catalyzed cross-coupling reaction of alkyl halides with biphenyl grignard reagent

Article abstract of DOI:10.14233/ajchem.2013.14469

In the presence of a catalytic amount of iron salts and N,N,N',N'-tetramethylethylene diamine as additive, alkyl bromide reacted with biphenyl magnesium bromide to obtain the cross-coupling product in good yields. The suitable amount of catalyst and the additive are 5 % mol (based on alkyl bromide), 1.3 equiv(based on alkyl bromide), respectively. Under the optimal conditions, the yields of the crosscoupling could reach up to 92.3 %.

Full text of DOI:10.14233/ajchem.2013.14469

Asian Journal of Chemistry; Vol. 25, No. 11 (2013), 6303-6305
http://dx.doi.org/10.14233/ajchem.2013.14469
Iron-Catalyzed Cross-Coupling Reaction of Alkyl Halides with Biphenyl Grignard Reagent
*
Z.Q. DAI, K.Q. LIU, Z.Y. ZHANG , B.M. WEI and J.T. GUAN
School of Chemical and Environmental Engineering, Wuhan Polytechnic University, Wuhan 430023, P.R. China
*
Corresponding author: Fax: +86 27 83943956; Tel: +86 13554263937; E-mail: zhiqundai@126.com
Received: 22 August 2012; Accepted: 8 May 2013)
(
AJC-13460
In the presence of a catalytic amount of iron salts and N,N,N',N'-tetramethylethylene diamine as additive, alkyl bromide reacted with
biphenyl magnesium bromide to obtain the cross-coupling product in good yields. The suitable amount of catalyst and the additive are
5 % mol (based on alkyl bromide), 1.3 equiv(based on alkyl bromide), respectively. Under the optimal conditions, the yields of the cross-
coupling could reach up to 92.3 %.
Key Words: Cross-coupling, Grignard reagent.
1
3
the H NMR spectra were measured in a CDCl solution with
INTRODUCTION
TMS as internal reference on aVarian MercuryVX-400 NMR
spectrometer. THF was purified by distillation from sodium
prior to use.
The cross-coupling of Grignard reagents with alkyl halides
catalyzed by metal is the important method for constructing
1-3
carbon-carbon bonds in organic synthesis . While the coupling
General procedure: A mixture of biphenylmagnesium
bromide 1 (0.9 M in THF, 65 mmol) and TMEDA (0.9 M in
THF, 65 mmol) was added to a mixture of alkyl halide 2a-i
4
reaction of alkyl halides with certain alkyl , phenyl or substi-
-7
8
-10
tuted phenyl Grignard reagents is known in the literature,
there have been no examples reported of this reaction using
biphenyl Grignard reagents. We have recently reported that
(
3
50 mmol) and FeCl (0.1 M in THF, 5 mol %) at -5 ºC. The
reaction mixture was stirred at -5 ºC for 0.5 h and after the
completion of the addition of biphenylmagnesium bromide
and TMEDA. 1 M HCl (50 mL) were added and extracted
with toluene (3 mL × 15 mL). The combined extracts were
1
1
12
CuCl
2
and CuI catalyzes the cross-coupling reaction of alkyl
bromides with biphenylmagnesium bromide in THF for 6 h,
the product, alkylbiphenyl, was obtained in high yield; however,
shorten the reaction time, unsatisfactory results were obtained.
During the course of our study on the cross-coupling reaction
4
dried over anhydrous MgSO . After evaporation of the solvent
under the reduced pressure and again the crude products were
purified by crystallization from ethanol or distilled under the
reduced pressure.
3
of biphenyl Grignard reagents, we have found that FeCl show
high catalytic reactivity for the cross-coupling reaction of alkyl
halides with biphenylmagnesium bromide, the cross-coupling
reaction was completed in very short time in high yields in the
1
4
-Ethylbiphenyl (3a): m.p. 34-35 ºC; H NMR (CDCl
3
,
δ ppm): 1.40 (t, 3H, -CH
3 2
), 2.52 (m, 2H, -CH -), 7.20-7.54
presence of catalytic amounts of FeCl
3
and N,N,N',N'-tetramethyl-
ethylene diamine (TMEDA) as an additive (Scheme-I).
-1
m, 9H, ArH); IR (KBr, νmax, cm ): 3010, 2950, 1600, 1505,
(
+
462, 1228, 805, 735; MS (50 eV) m/z (%): 182 (M , 100),
1
1
67 (75). Anal. calcd. (%) for C14
H14: C 92.31, H 7.69; found
FeCl3
MgBr + RX
TMEDA
(
%) C 92.26, H 7.73.
1
4-Propylbiphenyl (3b): b.p. 162-165 ºC/6 mm Hg; H
R
30 min
NMR (CDCl
3
, δ ppm): 1.06 (t, 3H, -CH
-Ar), 7.20-7.54 (m, 9H, ArH); IR (KBr,
max, cm ): 3050, 2895, 1605, 1508, 1456, 1280, 835, 730;
3 2
), 1.58 (m, 2H, -CH -
1
2a-i
3a-i
)
, 2.55 (t, 2H, -CH
2
Scheme-I
-1
ν
+
MS (50 eV) m/z (%): 196 (M , 100), 167 (65). Anal. calcd.
%) for C15H16: C 91.84, H 8. 16; found (%) C 91.86, H 8.11.
EXPERIMENTAL
(
Melting points were determined on a Laboratory Devices
Mel-temp apparatus and uncorrected. The IR spectra (KBr)
were recorded on a NICOLET 330 FT-IR spectrophotometer;
12
4
-Butylbiphenyl (3c): b.p. 140-141 ºC/3 mm Hg (Lit.
1
40 ºC/3 mmHg); H NMR (CDCl
1
3
, δ ppm): 0.91 (t, 3H,
-CH ), 1.34-1.42 (m, 2H, -CH -), 1.62-1.67 (m, 2H, -CH
3
2
2
-),

6
304 Dai et al.
Asian J. Chem.
2
.65 (t, 2H, -CH -Ar), 7.22-7.56 (m, 9H, ArH); IR (KBr, νmax
2
,
TABLE-1
CROSS-COUPLING REACTION OF
BIPHENYLMAGNESIUM BROMIDE WITH n-C H Br
12 25
-1
cm ): 3050, 2893, 1605, 1511, 1455, 1280, 835, 745; MS (50
+
eV) m/z (%): 210 (M , 100), 167 (85). Anal. calcd. (%) for
a
b
b
c
Entry FeCl (mol %)
3
Additive (equiv.)
None
Yield (%)
2.1
C
16
H18: C 91.37, H 8.63; found (%) C 91.44, H 8.66.
1
2
3
4
5
6
7
8
5
5
5
5
5
5
1
3
11
4
-Hexylbiphenyl (3d): m.p. 29-31 ºC (Lit. 29-32 ºC);
H NMR (CDCl , δ ppm): 0.83 (t, 3H, -CH ), 1.22-1.35 (m,
-), 1.59 (t, 2H, -CH -), 2.54 (t, 2H, -CH -Ar), 7.15-
Et N (1.3)
3
8.3
1
3
3
N-Methyl morpholine (1.3)
TMEDA(1.1)
6.5
85.2
92.3
88.4
86.7
90.1
6
7
1
H, -(CH
2
)
3
2
2
-1
TMEDA(1.3)
.58 (m, 9H, ArH); IR (KBr, νmax, cm ): 3045, 2923, 1605,
TMEDA(1.5)
501, 1438, 1240.
TMEDA(1.3)
11
4
-Octylbiphenyl (3e): m.p. 41-42 ºC (Lit. 41-42 ºC);
H NMR (CDCl , δ ppm): 0.87 (t, 3H, -CH ), 1.27-1.35 (m,
-), 1.60 (t, 2H, -CH -), 2.61 (t, 2H, -CH -Ar),
TMEDA(1.3)
1
a
3
3
Reaction conditions: n-C H Br (50 mmol), biphenyl magnesium
12 25
b
bromide (1.3 equiv, 0.9 M in THF), -5 ºC, 0.5 h. Based on n-C H Br.
1
7
1
0H, -(CH
2
)
5
2
2
12 25
c
Isolated yield.
-1
.25-7.60 (m, 9H,ArH); IR (KBr, νmax, cm ): 3026, 2863, 1601,
495, 1432, 1283.
11
4
-Nonylbipheny (3f): m.p. 44-46 ºC (Lit. 44-45 ºC);
H NMR (CDCl , δ ppm): 0.85 (t, 3H, -CH ), 1.25-1.31 (m,
-), 1.57 (m, 2H, -CH -), 2.63 (t, 2H, -CH -Ar),
TABLE-2
CROSS-COUPLING REACTION OF ALKYL HALIDES
1
3
3
a
WITH BIPHENYLMAGNESIUM BROMIDE
1
7
1
2H, -(CH
2
)
6
2
2
b
Entry Alkyl halides
C H -Br
Product
Yield (%)
90.1
-1
.22-7.53 (m, 9H,ArH); IR (KBr, νmax, cm ): 3020, 2885, 1600,
491, 1452, 1280.
C2H5
1
2
3
4
5
6
2
5
11
4
-Decylbiphenyl (3g): m.p. 52-53 ºC (Lit. 52-54 ºC);
H NMR (CDCl , δ ppm): 0.86 (t, 3H, -CH ), 1.25-1.34 (m,
-), 1.63 (t, 2H, -CH -), 2.65 (t, 2H, -CH -Ar),
(3a)
1
3
3
n -- C H7
3
1
7
1
4H, -(CH
2
)
7
2
2
n-C
3
H -Br
7
89.3
89.2
90.4
90.6
88.8
-1
(3b)
.25-7.53 (m, 9H,ArH); IR (KBr, νmax, cm ): 3045, 2945, 1601,
495, 1455, 1281.
n-C H
4
9
n-C H -Br
9
11
4
4
-Undecylbiphenyl (3h): m.p. 52-54 ºC (Lit. 53-54 ºC);
H NMR (CDCl , δ ppm): 0.85 (t, 3H, -CH ), 1.23-1.31 (m,
-), 1.52 (m, 2H, -CH -), 2.61 (t, 2H, -CH -Ar),
(3c)
1
3
3
nn -- C H
6
13
17
1
7
1
6H, -(CH
2
)
8
2
2
n-C H -Br
6 13
-1
.21-7.48 (m, 9H, ArH); IR(KBr, νmax, cm ): δ 3035, 2911,
(3d)
590, 1504, 1320, 854, 746.
n-
n-C H
8
11
n-C
8
H17-Br
4
-Dodecylbiphenyl (3i): m.p. 61-62 ºC (Lit. 61-62 ºC);
H NMR (CDCl , δ ppm): 0.89 (t, 3H, -CH ), 1.26-1.36 (m,
-), 1.62 (t, 2H, -CH -), 2.64 (t, 2H, -CH -Ar),
(3e)
1
3
3
nn -- C H
9 19
1
7
1
8H, -(CH
2
)
9
2
2
n-C H -Br
9 19
-1
.25-7.58 (m, 9H,ArH); IR (KBr, νmax, cm ): 3040, 2931, 1609,
(3f)
458, 854, 746.
nn -- C H
1
0
21
23
7
8
9
n-C H -Br
21
90.1
90.5
92.3
1
0
RESULTS AND DISCUSSION
(3g)
Initially, we performed the coupling reaction of biphenyl
nn -- C H
1
1
n-C H -Br
23
1
1
magnesium bromide with n-C12H25Br as a model reaction.
Selected results are shown in Table-1. Without any additive,
the product was obtained in only 2.1 % yield (Table-1, entry
(3h)
nn -- C H
2 25
1
n-C H -Br
25
1
2
1
). Under similar conditions, tertiary monoamines such as
triethylamine and N-methyl morpholine were ineffective
entries 2 and 3) and TMEDA showed high activity for this
cross-coupling reaction (entries 4-6). Optimization of the
reaction conditions using TMEDA and FeCl revealed that use
of 5 mol % FeCl (0.1 M in THF) and 1.3 equiv of TMEDA
0.9 M in THF) based on the halides at -5 ºC afforded coupling
(3i)
Reaction conditions: alkyl halides (50 mmol), biphenylmagnesium
bromide (1.3 quiv, 0.9 M in THF), TMEDA (1.3 equiv, 0.9 M in
a
(
b
THF), FeCl (0.1 M in THF, 5 mol %), -5 ºC, 0.5 h. Isolated yield.
3
3
Conclusion
3
(
3
For the first time, we have developed the FeCl /TMEDA
products in highest yield (entry 5).
catalyzed coupling reaction of biphenylmagnesium bromide
with alkyl bromide. Good to excellent yields of the coupling
products were obtained.
Further examination of the reaction conditions revealed
that slow addition of a mixture of the Grignard reagent and
the TMEDA to a solution of the halide and the iron catalyst
improves the product yield significantly. The mixture of the
Grignard reagent and TMEDA was added at such a rate that
the temperature of the react mixture was kept at -5 ºC. The
reaction mixture turns dark red and a greatly reduced yield is
obtained above 0 ºC. The scope of the reaction is illustrated in
Table-2.
ACKNOWLEDGEMENTS
The authors are grateful to the National Natural Science
Foundation of China (No. 11074054), Foundation of Hubei
Educational Commission (No. B20111702), Foundation of
Hubei Educational Commission for Distinguished Young
Scholars (No. Q20111740) for financial support.

Vol. 25, No. 11 (2013)
Iron-Catalyzed Cross-Coupling Reaction of Alkyl Halides with Biphenyl Grignard Reagent 6305
7
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J. Terao, H. Watanabe, A. Ikumi, H. Kuniyasu and N. Kambe, J. Am.
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