Efficient cyanation of aryl halide with K4[Fe(CN) 6]·3H2O catalyzed by a P-O bidentate chelate palladium complex under air

Article abstract of DOI:10.1002/aoc.3185

Cyanation of aryl halide with K₄[Fe(CN)₆] ·3H₂O has been carried out in the presence of a high-activity catalyst: an air-stable P-O bidentate chelate palladium complex. This method is applicable to both activated and deactivated aryl halides, and even a variety of aromatic nitriles are obtained in good yields under aerobic conditions. Copyright

Full text of DOI:10.1002/aoc.3185

Full Paper
Received: 3 May 2014
Revised: 18 May 2014
Accepted: 5 June 2014
Published online in Wiley Online Library: 7 July 2014
(wileyonlinelibrary.com) DOI 10.1002/aoc.3185
Efficient cyanation of aryl halide with K [Fe(CN) ]Á
4
6
3
H O catalyzed by a P–O bidentate chelate
2
palladium complex under air
Leiqing Fu, Xiaogang Li, Qiming Zhu, Sanbao Chen, Yanping Kang
and Mengping Guo*
Cyanation of aryl halide with K
P–O bidentate chelate palladium complex. This method is applicable to both activated and deactivated aryl halides, and even
4
[Fe(CN)
6
]Á3H
2
O has been carried out in the presence of a high-activity catalyst: an air-stable
a variety of aromatic nitriles are obtained in good yields under aerobic conditions. Copyright © 2014 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web-site.
Keywords: aryl halide; cyanation; palladium complex; catalysis; synthesis
were complex and difficult to synthesize. There was no doubt
that the catalyst was extremely expensive. As a result, we
Introduction
Aryl nitriles are of significant interest in organic chemistry. The
versatile transformations of the nitrile function make them im-
portant intermediates in the synthesis of polyamides, amidines,
propose an air-stable, simple-structured and highly active P–O
bidentate chelate palladium complex (Scheme 1), which has
proved to be very effective in the Pd-catalyzed Suzuki coupling
[
1,2]
[23]
imidoesters and biologically active molecules.
nitriles themselves were an integral part of herbicides, pesticides,
Moreover, aryl
reaction in aqueous solvents at room temperature, and report
the efficient catalytic cyanation of aryl halides including aryl
chlorides with K [Fe(CN) ]Á3H O.
[
3]
dyes, natural products and pharmaceuticals. In the past, the
cyanide sources used in cyanation reactions were alkali metal cy-
anides (KCN or NaCN), acetone cyanohydrin, trimethylsilylcyanide
4
6
2
[
4]
(
TMSCN) and Zn(CN)
2
.
Traditional synthetic methods for the
Results and Discussion
[
5]
formation of aryl nitriles were the Rosenmund–von Braun and
[6]
the Sandmeyer
reactions and the industrially applied
An initial reaction condition screening was performed using the
[7]
ammoxidation. The limited substrate scope of these reactions
drove chemists to explore alternative transition-metal-catalyzed
cyanation reactions for the preparation of more diversely
model cyanation reaction of 4-chloroacetophenone with K [Fe
4
(CN) ]Á3H O. In this study the performances of various solvents,
6
2
bases and catalyst loadings were examined. Typical results are
listed in Table 1. First, we investigated the effect of solvent. As
shown in Table 1, an investigation of the influence of the solvent
suggests that DMF is the best choice. An 80% yield of
4-acetylbenzonitrile is obtained under the reaction conditions in
this case (Table 1, entry 8). Furthermore, this result prompted us
to study various bases in order to find the best base to use in
the reaction. We find that similar yields are obtained when
NaOAcÁ3H O and K PO Á3H O are used (Table 1, entries 12 and
[
8]
[9]
[10]
substituted aromatic nitriles. Copper, nickel and palladium
complexes are known to be effective catalysts for this reaction.
Consequently, significant research effort has been focused on
the preparation and use of catalysts capable of activating this reac-
tion. To date, some auxiliary ligands and palladium catalysts, such
[
11]
[12,13]
as ligand-free palladium salts, palladacycles
ligands,
and phosphine
[14,15]
[16,17]
and microwave-promoted reactions have been
developed in order to enable cyanation to be performed under
mild reaction conditions, with a good substrate scope.
2
3
4
2
16). We also find that 1.0 mol% of the catalyst is enough to drive
the reaction to completion (Table 1, entry 18). But it is unfavor-
able to the reaction if we continue to reduce the amount of cat-
alyst: we obtain a low yield of 73% (Table 1, entry 19).
Interestingly, the catalytic system does not require the assistance
of amine ligands (TMEDA, DBU, etc.) and troublesome solvents
Recently, K [Fe(CN) ]Á3H O has been used as a cheap and envi-
4
6
2
ronment friendly cyanation reagent for catalyzed cyanation of
aryl halides. In 2004, Beller and co-workers described the first
cyanation of aryl halides with K
4
[Fe(CN)
6
]Á3H
2
O for the prepara-
[
18]
tion of aromatic nitriles.
been limited to aryl bromides or iodides.
of aryl chlorides had been reported by some authors,
of the aryl chlorides were activated aryl chlorides. To the best
of our knowledge, a few efficient methods involving K [Fe(CN)
O have been reported for the cyanation of aryl chlorides,
However, all these methods have
[
19,20]
Even if cyanation
[
21,22]
most
*
Correspondence to: Mengping Guo, Key Laboratory of Jiangxi University for
Applied Chemistry and Chemical Biology, Yichun University, Yichun 336000,
People’s Republic of China. E-mail: guomengping65@163.com
4
6
]Á3H
2
but the reaction conditions were harsh. The serious shortcomings
were that the structures of the catalysts used in these reactions
Key Laboratory of Jiangxi University for Applied Chemistry and Chemical Biology,
Yichun University, Yichun 336000, People’s Republic of China
Appl. Organometal. Chem. 2014, 28, 699–701
Copyright © 2014 John Wiley & Sons, Ltd.

L. Fu et al.
Table 2. Cyanation of aryl halides with K
by P–O bidentate chelate palladium complex
4
[Fae(CN)
6
]Á3H
2
O catalyzed
Scheme 1. Synthesis of P–O bidentate chelate palladium complex.
b
Entry
R
X
Yield (%)
Table 1. Cyanation of 4-chloroacetophenone with K
catalyzed by P–O bidentate chelate palladium complex
4
[Fae(CN)
6
]Á3H
2
O
1
2
3
4
5
6
4-COMe
4-OMe
4-H
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
Br
Br
93
62
88
85
83
81
98
84
95
93
91
92
87
90
2-Me
2,6-Me
2
4-CO H
b
c
Entry Solvent
Base
Catalyst (mol%) Yield (%)
7
4-COMe
4-OMe
4-H
8
9
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
NMP
DMAc
THF
K
K
K
K
K
K
K
K
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
2
1
0.5
0
Trace
38
1
1
1
1
1
0
1
2
3
4
2-Me
2,6-Me
TMEDA
TMSCN
t-BuOH
MeCN
DMF
53
2
4-CO H
Trace
49
4-CO-Ph
d
1-Naphthalene
65
a
80
Reaction conditions: 1.0mmol of substrate, 0.3mmol of K
O, 1.0 mol% catalyst, 3.0 mmol of K PO O and 2.0ml of
Á3H
DMF, 130 °C for 16h.
4
6
[Fe(CN) ]Á
3
H
2
3
4
2
DMF
KOH
64
0
1
2
3
4
5
6
7
8
9
DMF
Et
Na
3
N
70
b
Isolated yield was based on the aryl halide.
DMF
2
CO
3
68
c
Aryl halide is aryl bromide and reaction time is 12 h.
DMF
NaOAcÁ3H
NaOH
2
O
89
d
Aryl halide is 1-halogenated naphthalene.
DMF
66
DMF
NaF
66
DMF
Na
3
PO
4
77
DMF
K
3
K
3
K
3
K
3
PO
4
PO
4
PO
4
PO
4
Á3H
2
2
2
2
O
O
O
O
92
Table 3. Cyanation of pyridyl halide with K
by P–O bidentate chelate palladium complex
4
[Fe(CN)
6
]Á3H
2
O catalyzed
DMF
Á3H
Á3H
Á3H
90
DMF
89
DMF
73
a
Reaction conditions: 1.0 mmol of 4-chloroacetophenone, 0.3 mmol
of K [Fe(CN) O, 2.0 ml of solvent, 3.0 mmol of base, 130 °C
]Á3H
for 16 h.
Isolated yield was based on the aryl chlorides.
4
6
2
b
b
Entry
R
X
Yield (%)
a
1
H
H
Cl
Br
Trace
78
c
2
[24]
(
NMP, DMAc, etc.). Furthermore, that Pd black formation is not
a
Reaction conditions: 1.0 mmol of 2-chloropyridine, 0.3 mmol of K
Fe(CN) O, 1.0 mol% catalyst, 3.0 mmol of K PO Á3H O and
]Á3H
.0 ml of DMF, 130 °C for 16 h.
Isolated yield was based on the pyridyl halide.
4
observed in the course of the reaction suggests that our catalytic
system is perfectly stable to air.
[
2
6
2
3
4
2
After optimizing the reaction conditions, we studied the scope
and the possible limitations of this reaction including typical aryl
bromides (Table 2). Under the same reaction conditions, the
cyanation of aryl bromides only needs 12 h (Table 2, entries 7–14).
Remarkably, the steric hindrance of substrates has little effect on this
cyanation reaction. 2-Chlorotoluene, 2,6-dimethylchlorobenzene
and 1-bromonaphthalene afford products in good to excellent
yields (Table 2, entries 4, 5, 10, 11 and 14). As expected, activated aryl
halides are smoothly converted into the corresponding products in
good yields (Table 2, entries 1, 6, 7, 12 and 13). Electron-rich aryl
halides are generally less reactive and their reactions proceed
incompletely even for prolonged time and at higher reaction
temperature (Table 2, entries 2 and 8). Unfortunately, the isolated
yield of the reaction of 2-bromopyridine is 78% (Table 3, entry 2)
while that of 2-chloropyridine is just a trace (Table 3, entry 1)
because of a large amount of by-products produced by the reaction.
b
c
Pyridyl halide is 2-bromopyridine and reaction time is 12 h.
Experimental
The P–O bidentate chelate palladium complex was prepared
according to a literature procedure.
[
23]
A mixture of aryl halide
(1.0 mmol), K [Fe(CN) ]Á3H O (0.3 mmol), K PO Á3H O (3.0 mmol),
4
6
2
3
4
2
DMF (2.0 ml) and catalyst (1.0 mol%) was stirred at 130 °C in air.
The reaction mixtures of aryl chlorides were stirred for 16 h while
those of aryl bromides were stirred for 12 h, and then quenched
with water. The mixture was diluted with dichloromethane. The
organic layer was separated and the aqueous layer was extracted
with dichloromethane (3 × 10 ml). The combined organic phase
was dried with Na SO . After filtering, the solvent was removed
2
4
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Copyright © 2014 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2014, 28, 699–701

Cyanation of aryl halide catalyzed by a bidentate chelate palladium complex
[
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[
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We developed an efficient method for the cyanation of aryl chlorides
and aryl bromides with the environmentally benign cyanide source
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[
[
[
K
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[Fe(CN)
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]Á3H
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and aryl bromides could be successfully converted into the correspond-
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We are grateful to the National Natural Science Foundation of China
(no. 21063015), Jiangxi Provincial Natural Science Foundation of
China (no. 20114BAB203012) and the Key Science and Technology
[
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Additional supporting information may be found in the online
version of this article at the publisher’s web-site.
Appl. Organometal. Chem. 2014, 28, 699–701
Copyright © 2014 John Wiley & Sons, Ltd.
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