Cul/1,10-phenanthroline: An efficient catalyst system for the cyanation of aryl halides

Article abstract of DOI:10.3184/030823407X237812

Aryl nitriles have been prepared in good yields from the corresponding aryl halides with potassium hexacyanoferrate(II) using Cul/1,10-phenanthroline as the catalyst system. Furthermore, the reaction is compatible with a wide range of functional groups including nitro and carbonyl substituents.

Full text of DOI:10.3184/030823407X237812

484 RESEARCH PAPER
AUGUST, 484–485
JOURNAL OF CHEMICAL RESEARCH 2007
CuI/1,10-phenanthroline: An efficient catalyst system for the cyanation of
aryl halides
Yi-Zhong Zhu and Chun Cai*
Chemical Engineering College, Nanjing University of Science & Technology, Nanjing 210094, China
Aryl nitriles have been prepared in good yields from the corresponding aryl halides with potassium
hexacyanoferrate(II) using CuI/1,10-phenanthroline as the catalyst system. Furthermore, the reaction is compatible
with a wide range of functional groups including nitro and carbonyl substituents.
Keywords: copper(I) catalysis, 1,10-phenanthroline, cyanation, potassium hexacyanoferrate(II), aryl nitrile
Aryl nitriles are of considerable interest as an integral part
of pharmaceuticals, herbicides, natural products and dyes.1
In addition, nitriles play a crucial role as they can be easily
converted into a variety of functional groups such as acids,
ketones, oximes and amines.2
Table 1 Evaluation of various reaction conditionsa
Entry Cu/mol%
Ligandb
Additive/mol%
Yield/%c
1
2
CuI(10)
CuI(10)
CuI(10)
CuI(10)
CuI(10)
CuI(20)
CuI(20)
CuI(20)
CuI(20)
CuI(20)
CuI(20)
CuCl(20)
CuBr(20)
Cu2O(10)
Cu (20)
BIPY
KI(20)
50
51
7
1,10-phen
TMEDA
DABCO
KI(20)
3
KI(20)
In general, the most common and direct method for the
introduction of the cyano group is via cyanation of the parent
aryl halides. Since the discovery of transition metal catalysed
cross-coupling reactions, a great deal of interest has been
devoted to the development of a practical version of this
transformation.3 Until now, a number of successful palladium-
and nickel-catalysed protocols have been reported.4,5 However,
the major disadvantages associated with the broad application
of currently known palladium- and nickel-catalysed protocols
are the high cost of these metals and the need for using
expensive and toxic phosphines as ligands. This makes the
development of methods using Cu catalysts quite attractive.
Until now, most of the work has concentrated on the
inconvenient traditional cyanide sources such as alkali
cyanides,2b zinc cyanide, trimethylsilyl cyanide, and acetone
cyanohydrin. However, these cyanide sources all have some
severe drawbacks. In order to avoid these problems, potassium
hexacyanoferrate(II) was rediscovered as a non-toxic cyanide
source by Beller.4g Nevertheless, only two reports described
the cyanation catalysed by Cu catalysts using potassium
hexacyanoferrate(II) as cyanide source.6,7 Although applying
4
KI(20)
Trace
11
75
55
35
75
54
85
26
39
41
40
5
–
KI(20)
6
1,10-phen
1,10-phen
1,10-phen
1,10-phen
BIPY
KI(20)
7
PEG-400(20)
8
PEG400(20), KI(20)
9
–
–
–
–
–
–
–
10
11d
12d
13d
14d
15d
1,10-phen
1,10-phen
1,10-phen
1,10-phen
1,10-phen
aReaction conditions: 3.0 mmol bromobenzene, 40 mol% dry
K4[Fe(CN)6], 5 ml DMAc, 100 mol% Na2CO3, 140°C, 24 h.
b80mol%;BIPY=2,2'-bipyridine,1,10-phen=1,10-phenanthroline,
TMEDA = N,N,N',N'-tetramethyl ethylenediamine, DABCO = 1,4-
diazabicyclo[2.2.2]octane.
cYields were determined by GC with 1,3-dimethoxybenzene as
the internal standard.
d60 mol% dry K4[Fe(CN)6] was used.
[2.2.2]octane (DABCO) have also been employed in this
reaction and none of them gave a higher yield than BIPY and
1,10-phen (entries 3 and 4).Ablank test without ligand afforded
benzonitrile only in a poor yield of 11% (entry 5), which
suggested that the ligand was the key factor in obtaining the
corresponding aryl nitriles. When 20 mol% of CuI was used,
a good yield of 75% of benzonitrile was obtained (entry 6).
Attempts to add PEG-400 decreased the product yield (entries
7 and 8). To our surprise, cyanation without additive also gave
a similar yield to the cyanation using 20 mol% KI as additive
(entry 9). This catalyst system was unlike previously reported
Cu(BF4)2·6H2O
and
N,Nꢀ'-dimethyl
ethylenediamine
(DMEDA) as the catalyst system was reported, the process
used KI as additive to make the cyanation work effectively.6
Subsequently, Beller and co-workers demonstrated CuI/N-
alkylimidazole as the catalyst system for the cyanation of
heteroaryl halides without the use of KI as additive.7 However,
two equivalents of ligand (N-alkylimidazole) was needed
in the reaction. Very recently, 1,10-phenanthroline and its
derivatives as ligands have been successfully used in copper-
catalysed coupling reactions.8 To further expand easier and
safer methods for cyanation reactions, nontoxic copper(I)-
catalysed cyanation can still attract current interest. Herein,
our efforts have shown that the cyanation of aryl halides
with K4[Fe(CN)6] can be efficiently catalysed by CuI in the
presence of 1,10-phenanthroline.
As a starting point for the development of our cyanation
system, the reaction of bromobenzene with K4[Fe(CN)6]9 was
investigated. Variation of reaction conditions on this model
reaction is shown in Table 1. The reaction was first attempted
using 3 mmol bromobenzene, 40 mol% dry K4[Fe(CN)6],
1.0 equivalent of Na2CO3, 10 mol% CuI, 20 mol% KI, 0.8
equivalent of 2,2'-bipyridine (BIPY) as the ligand in DMAc.
Amoderate yield of 50% of benzonitrile was obtained (entry 1).
Using 1,10-phenanthroline (1,10-phen) as ligand led to a
similar effect (entry 2). Other ligands, such as N,N,Nꢀ',N'-
tetramethyl ethylenediamine (TMEDA) and 1,4-diazabicyclo
Table 2 Cyanation of bromobenzene in the presence of
different bases and solventsa
Entry
Base
Solvent
Yield/%b
1
Na2CO3
K2CO3
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMF
85
51
13
41
2
3
KOH
4
CH3COONa
CH3CH2ONa
t-BuOK
HCOONa
K3PO4·3H2O
KF
5
Trace
12
6
7
13
8
30
9
55
10
11
Na2CO3
Na2CO3
67
NMP
63
aReaction conditions: 3.0 mmol bromobenzene, 60 mol%
dry K4[Fe(CN)6], 20 mol% CuI, 5 ml solvent, 100 mol% base,
80 mol% 1,10-phen, 140°C, 24 h.
bYields were determined by GC with 1,3-dimethoxybenzene as
the internal standard.
* Correspondent. E-mail: c.cai@mail.njust.edu.cn
PAPER: 07/4624

JOURNAL OF CHEMICAL RESEARCH 2007 485
Table 3 Copper-catalysed cyanation of various aryl halidesa
To conclude, we report a copper(I)-catalysed method for
the cyanation of aryl bromides and iodides using potassium
hexacyanoferrate(II). The cyanide source is non-toxic and
inexpensive. Furthermore, this protocol is palladium-free
and avoids the use of expensive and/or air-sensitive ligands.
A variety of aryl halides give the corresponding benzonitriles
in good to excellent yields.
R
R
CuI/1,10-Phen
K4[Fe(CN)6]
X
CN
2
1
N
N
1,10-Phen
Entry
Ar-X
1
Yield/%b
of 2
Experimental
General procedure for the cyanation of aryl halides: After standard
cycles of evacuation and filling with dry and pure nitrogen, an oven-
dried tube was charged with CuI (0.6 mmol), 1,10-phenanthroline
(2.4 mmol), Na2CO3 (3 mmol), aryl halide (3 mmol) and DMAc
(5 ml). The tube was evacuated and filled with nitrogen. Then the
tube was sealed and the mixture was stirred at 140°C for 24 h.
After cooling to room temperature, the mixture was diluted with ethyl
acetate (30 ml) and filtered. Then 1,3-dimethoxybenzene (400 μl) was
added as the internal standard for chromatography. The filtrate was
washed with water (3 × 15 ml) and analysed by gas chromatography.
The GC yields were determined by obtaining correction factors using
authentic samples of the expected products.
For isolating the products: After the reaction was completed, the
mixture was diluted with ethyl acetate (30 ml) and filtered. The filtrate
was washed with water (3 × 15 ml). The organic phase was dried over
Na2SO4, filtered and concentrated under reduced pressure. Finally,
the product was isolated by flash chromatography on silica gel with
EtOAc–petroleum ether as the eluent. All prepared benzonitriles are
known commercial compounds and were identified by GC–MS.
1
2
b-bromonaphthalene
p-CH3COC6H4Br
p-FC6H4Br
83 (78)
85 (81)
81
80 (72)
81 (75)
83
78
61 (53)
52
47
99
99 (92)
96
99 (93)
84
3
4
p-O2NC6H4Br
p-CF3C6H4Br
m-CF3C6H4Br
p-CH3C6H4Br
p-CH3OC6H4Br
o-CH3OC6H4Br
p-H2NC6H4Br
C6H5I
5
6
7
8
9
10
11
12
13
14
15
16
17c
o-CH3C6H4I
m-CH3C6H4I
p-CH3C6H4I
o-O2NC6H4I
p-O2NC6H4I
87 (76)
Trace
p-CF3C6H4Cl
aReaction conditions: 3.0 mmol aryl halide, 20 mol% CuI,
60 mol% dry K4[Fe(CN)6], 5 ml DMAc, 100 mol% Na2CO3,
80 mol% 1,10-phen, 140°C, 24 h.
Receivedꢀ7ꢀAprilꢀ2007;ꢀacceptedꢀ30ꢀJulyꢀ2007ꢀ
Paperꢀ07/4624ꢀ doi:ꢀ10.3184/030823407X237812
bYields were determined by GC with 1,3-dimethoxybenzene as
the internal standard. Numbers in parentheses show isolated
yields. All prepared benzonitriles are commercially available.
cThe nitrile was not observed even after 36 h (150°C).
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2
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of this copper-catalysed system was insufficient to drive the
reaction to occur even at higher reaction temperature and
prolonged reaction time (entry 17).
9
K4[Fe(CN)6]·3H2O is ground to a fine powder and dried under a high
vacuum at 80°C overnight.
PAPER: 07/4624