Stable palladium nanoparticles catalyzed synthesis of benzonitriles using K4[Fe(CN)6]

Article abstract of DOI:10.1016/j.tetlet.2014.11.051

A stable palladium nanocatalyst is used in the synthesis of benzonitriles by cyanation of aryl iodides. A nontoxic and economic potassium hexacyanoferrate was used as a safe cyanide source. A variety of benzonitriles are efficiently synthesized using the stable nanocatalyst. The catalyst was quantitatively recovered and reused without any apparent loss in the catalytic activity.

Full text of DOI:10.1016/j.tetlet.2014.11.051

Accepted Manuscript
Stable palladium nanoparticles catalyzed synthesis of benzonitriles using
K4[Fe(CN)6]
Dhandapani Ganapathy, Surya Srinivas Kotha, Govindasamy Sekar
PII:
S0040-4039(14)01944-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.11.051
TETL 45435
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
17 September 2014
9 November 2014
13 November 2014
Please cite this article as: Ganapathy, D., Kotha, S.S., Sekar, G., Stable palladium nanoparticles catalyzed synthesis
of benzonitriles using K4[Fe(CN)6], Tetrahedron Letters (2014), doi: http://dx.doi.org/10.1016/j.tetlet.2014.11.051
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
Leave this area blank for abstract info.
Stable Palladium Nanoparticles Catalyzed
Synthesis of Benzonitriles Using K4[Fe(CN)6]
D. Ganapathy, K. Surya Srinivas and G. Sekar*

1
Tetrahedron Letters
journal homepage: www.els evier.com
Stable Palladium Nanoparticles Catalyzed Synthesis of Benzonitriles Using
K4[Fe(CN)6]
Dhandapani Ganapathya Surya Srinivas Kothaa and Govindasamy Sekara*
aDepartment of Chemistry, Indian Institute of Technology Madras, Chennai, Tamil Nadu – 600036, India
Fax: +91(44)22574202, E-mail: gsekar@iitm.ac.in.
ABSTRACT
Article history:
Received
A stable palladium nanocatalyst is used for the synthesis of benzonitriles by cyanation of aryl
iodides. A nontoxic and economic potassium hexacyanoferrate was used as safe cyanide source.
A variety of benzonitriles are efficiently synthesized using the stable nanocatalyst. The catalyst
was quantitatively recovered and reused without any apparent loss in the catalytic activity.
Received in revised form
Accepted
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Stable palladium nanoparticles
Pd-C covalent bonds
Cyanation
K4[Fe(CN)6]
Recyclable Catalyst
Benzonitriles are important structural unit of various natural
products, agrochemicals, biologically active compounds and
dyes.1,2 Benzonitriles are the key intermediates in preparation of
several drugs.3 Nonionic surfactants emulsified with benzonitriles
are used as dyeing agents.4 Conjugated polymer and polynitriles,
synthesized from benzonitriles are utilized in the preparation of
laser diodes and fiber optics.5 In addition, benzonitriles are the
key intermediate in synthetic organic chemistry.6 They are
readily converted into several other functional groups such as
amines, aldehydes, acids and amides. Moreover, benzonitriles are
the industrially important solvent to carry out several organic
reactions.
highly toxic and hence the industrial application of the reaction is
often limited. Cyanation of aryl halides using safe cyanide source
has gained much interest for the synthesis of benzonitriles.
Recently, Beller et al. reported the use of K4[Fe(CN)6] as a safe
cyanide source for cyanation of aryl halides.14 K4[Fe(CN)6] is
non-toxic compared to other cyanide ion source and all the
cyanide groups from the iron centre can be coupled with aryl
halides.15 In addition, K4[Fe(CN)6] is non-hygroscopic,
commercially available, easy to handle and very economic. In
general, transition metal catalyst may be deactivated by the
formation of stable cyanide complex with transition metal.
However, in the case of K4[Fe(CN)6], slow release of cyanide
ions allows the metal catalyst to improve the efficiency.
Benzonitriles are traditionally syntheisized via ammoxidation
of toluene,7 Rosenmund von Braun reaction,8 and diazotization of
anilines followed by Sandmeyer reaction.9 However, these
procedures associated with major disadvantages of using high
reaction temperature, stoichiometric amount of copper(I) cyanide
as cyanating agent and production of large amount of heavy
metal waste after the final reaction. Transition metal catalyzed
cyanation of aryl halides for the synthesis of benzonitriles using
cyanting agents are the most efficient and reliable method.10 Pd,
Cu, Ni, Rh and Ir are the most common transition metal catalysts
used for the cyanation of aryl iodides. Particularly, palladium
catalysts are being the most predominently used one for the
cyanation reaction because of wide functional groups tolerance.11
First report on the cyanation of aryl halides was documented by
Takagi et al. using palladium catalyzst in 1973, where they used
In recent years, palladium nanoparticles (Pd NPs) have been
perceived as
a
powerful catalyst for several organic
transformations.16 Requriement of low catacatalytic loading,
providing high selectivity and recactivitydue to larger surface
area are the visible advantage of Pd-NPs as catalyst.17 Recently,
cyanation of aryl halides using K4[Fe(CN)6] catalyzed by Pd NPs
gained much importance in the synthesis of benzonitriles due to
the ease separation and reusability of the catalyst.18 Very
recently, we have reported synthesis and application of new type
of easily recoverable and reusable stable palladium nanoparticles
(Pd-BNPs) stabilized by metal-carbon covalent bond.19 Herein,
we report an efficient stable Pd-BNPs catalyzed phosphine free
synthesis of benzonitriles using non-toxic, safe, commercially
available and economic cyanide ion source of K4[Fe(CN)6]
(Scheme 1).
o
KCN as cyanating agent at 140-150 C.12 Later, several other
cyanide ion sources such as CuCN, KCN, NaCN, CuSCN and
Zn(CN)2 are used for the cyanation in the presence of various
palladium catalyst.13 However, many of the cyanide sources are

2
Tetrahedron Letters
amount of product was observed. It is concluded from these
o
optimization studies that K3PO4, in DMF solvent at 120 C was
turned out to be the best choice of reaction condition for the
cyantion reaction with K4[Fe(CN)6].
Table 2. Pd-BNPs catalyzed cyanation of aryl iodides using
K4[Fe(CN)6].
Scheme 1 Pd-BNPs catalyzed synthesis of benzonitriles using
K4[Fe(CN)6]
Initial investigation for the synthesis of benzonitriles by the
cyanation of aryl iodides was started with the reaction of 4-
iodotoluene 1 and K4[Fe(CN)6] in the presence of Pd-BNPs and
o
K2CO3 in acetonitrile at 120 C. The reaction afforded 60% of 4-
methylbenzonitrile 2 in 3 hours. Encouraged by this initial result,
several bases were screened and the results are summarized in the
Table 1.0. When K2CO3 was replaced with Cs2CO3, the yield was
increased to 75% (Entry 2). Strong base such as KOH reduced
the yield drastically to 10% (Entry 3). Usage of organic base such
as Et3N afforded only 20% yield under the same reaction
conditions (Entry 4). When the base was changed to K3PO4, the
yield has significantly increased to 87% (Entry 5). It has been
reported in the literature that the efficiency of the cyantion of aryl
halides can be increased by the use of additives such as amines.
However, when the reaction was carried out with 2 equiv. of
Et3N and K3PO4, only 65% of the cyanation product was isolated
(Entry 6). Finally, the K3PO4 was turned out to be the choice of
base in CH3CN at 120 oC for the cyanation reaction (Entry 5).
Table 1. Screening of bases and solvents for cyanation of aryl
iodides using K4[Fe(CN)6] catalyzed by stable Pd-BNPs.
To improve the efficiency of the cyanation of aryl iodides
with K4[Fe(CN)6] and Pd-BNPs, the reaction was subjected to
several solvents. Among the solvents screened, the non-polar
solvents such as toluene and xylene afforded only trace amount
of cyanated product (Table 1, Entries 10 and 11). When the
solvent was changed from acetonitrile to DMF, the yield was
significantly increased to 92% (Entry 12). Other solvents such as
DMA and dioxane afforded 82% and 30% of yield, respectively
(Entries 13 and 14). When the reaction was carried out with
mixture of solvents such as water and acetonitrile, only trace
Having the successful optimized reaction conditions in hand,
investigation of the substrate scopes for the cyanation reaction

3
has started. Several benzonitriles were synthesized by the
cyanation of aryl iodides and the result is summeraized in the
Table 2. Electron-releasing, electron-withdrawing and sterically
hindered aryl iodides were well tolerated under the optimized
reaction conditions. Sterically hindered and electron rich o-
methoxy iodobenzene gave 87% of yield (Entry 3). o-Methyl
iodobenzene yielded 91% of yield within 2 hours (Entry 2). 4-
tert-Butyl substituted iodobenzene yielded 82% of 4-(tert-
butyl)benzonitrile. Strong electron-withdrawing group such as
nitro group provided 98% nitro benzonitriles in very short
reaction time of 1 hour (Entry 7 and 8). Similarly, electron rich o-
iodo aminobenzene and o-iodo phenol yielded the cyanated
product 87 and 88%, respectively (Entries 10 and 11).20
catalyst for the other important organic transformation is under
progress.
Acknowledgment
We thank DST nanomission (SR/NM/NS-1034/2012(G)) New
Delhi for financial support. DGP and KSS thanks CSIR, India for
senior research fellowship.
Supporting data
Supplementary data (representative experimental procedures,
characterization data, and copies of NMR) associated with this
article can be found, in the online version.
References
After the successful development of cyanation of aryl iodides
by stable Pd-BNPs, the catalytic recycling was investigated using
the reaction of 4-iodotoluene with K4[Fe(CN)6] under optimized
reaction condition.21 After the completion of cyanation reaction,
the reaction mixture was cooled to room temperature and diluted
with ethanol and water, resulted solid residue was recovered by
centrifugation. The collected solid particles were washed with
water, ethanol and dried. The recovered catalyst was reused for
the cyantion reaction. The catalyst was reused five times without
any significant loss in the catalytic activity (Figure 1). This is in
agreement with HRTEM analysis as the Pd-BNPs showed same
particle size without any obvious agglomeration even after fifth
catalytic cycles (Figure 2).
(1)
(2)
(3)
Kleemann A, Engel J, Kutscher B, Reichert DGeorg Thieme, 2001
Collier, S. J.; Langer, P., Sci. Synth. 2004, 19, 403-425.
Tao, K.; Zhou, Y.; Zhang, J. Zhongguo Yiyao Gongye Zazhi 2005, 36
(2), 65-67.
(4)
(5)
(6)
(7)
(8)
Von Brachel, H.; Cornelius, D.; Herrmann, E.; Graewinger, O.;
Cassella Farbwerke Mainkur A.-G. . 1970, p 10 pp.
Zhao, X.; Hu, X.; He, Y.; Chen, H. Polym. Eng. Sci. 2000, 40 (12),
2551-2557.
Rappoport Z. “Chemistry of the Cyano Group”. 1st Ed. London: John
Wiley & Sons, 1970.
Martin, A.; Kalevaru, N. V.; Luecke, B.; Sans, J. Green Chem. 2002,
4 (5), 481-485.
(a) Bacon, R. G. R.; Hill, H. A. O. J. Chem. Soc. 1964, 1097-1107;
(b) Lindley, J., “Copper-assisted nucleophilic substitution of aryl
halogen”. Tetrahedron 1984, 40 (9), 1433-56. (c) Rosenmund, K. W.;
Struck, E. Ber. Dtsch. Chem. Ges. B 1919, 52B, 1749-56.
Sandmeyer, T., Ber. 18, 1492-96.
(9)
(10)
(11)
Yan, G.; Yu, J.; Zhang, L. Youji Huaxue 2012, 32 (2), 294-303.
(a) Sekiya, A.; Ishikawa, N. Chem. Lett. 1975, 3, 277-8; (b)Dalton, J.
R.; Regen, S. L. J. Org. Chem. 1979, 44 (24), 4443-4; (c) Chatani, N.;
Hanafusa, T. J. Org. Chem. 1986, 51 (24), 4714-16; (d) V. Nair, D. F.
Purdy, T. B. Sells, J. Chem. Soc., Chem. Commun. 1989, 878879; (e)
D. M. Tschaen, R. Desmond, A. O. King, M. C. Fortin, B. Pipik, S.
King, T. R. Verhoeven, Synth. Commun. 1994, 24, 887890; (f) Zhang,
G.-Y.; Yu, J.-T.; Hu, M.-L.; Cheng, J. J. Org. Chem. 2013, 78 (6),
2710-2714; (g) Zhang, Z.; Liebeskind, L. S. Org. Lett. 2006, 8 (19),
4331-4333; (h) Sundermeier, M.; Zapf, A.; Beller, M. Angew. Chem.,
Int. Ed. 2003, 42 (14), 1661-1664; (i) Zheng, S.; Yu, C.; Shen, Z.
Org. Lett. 2012, 14 (14), 3644-3647.
Figure 1. Catalytic recycles of Pd-BNPs for the cyanation of aryl
halides.
(12)
(13)
Takagi, K.; Okamoto, T.; Sakakibara, Y.; Oka, S., Chem. Lett. 1973,
(5), 471-4.
a
b
(a) Anbarasan, P.; Schareina, T.; Beller, M. Chem. Soc. Rev. 2011, 40
(10), 5049-5067; (b) Sundermeier, M.; Zapf, A.; Beller, M. Eur. J.
Inorg. Chem. 2003, 19, 3513-3526.
(14)
(15)
Schareina, T.; Zapf, A.; Beller, M. Chem. Commun. 2004, 12, 1388-
1389.
Schareina, T.;. Zapf, A.; Beller, M.; J. Organomet. Chem., 2004,689,
4576–4583.
(16)
(17)
Moreno-Manas, M.; Pleixats, R. Acc. Chem. Res. 2003, 36, 638.
(a) Balanta, A.; Godard, C.; Claver, C. Chem. Soc. Rev. 2011, 40,
4973; (b) Durand, J.; Teuma, E.; Gomez, M. Eur. J. Inorg. Chem.
2008, 3577; (c) Astruc, D. Inorg. Chem. 2007, 46, 1884.
(a) Polshettiwar, V.; Hesemann, P.; Moreau, J. E.; Tetrahedron, 2007,
63, 6784–6790; (b) Chattopadhyay, K.;Dey, R.; Ranu, B. C.;
Tetrahedron Letters, 2009, 50 3164–3167; (c) Beletskayab, I. P.;
Selivanovaa, A. V.; Tyurina, V. S.; Matveeva, V. V.; Khokhlovb, A.
Figure 2. HRTEM images of Pd-BNPs before catalytic (a) and after the
catalytic cycles (b).
Conclusion
(18)
A very stable Pd-BNPs were used as catalyst for the cyanation
of aryl iodides using non-toxic, economic and commercially
available K4[Fe(CN)6]. Several aryl iodides were converted into
benzonitriles with good to excellent yield. The Pd-BNPs were
successfully recovered and reused three times without any
appreciable loss in the particle size and reactivity. Very
importantly, the reaction offers a method for the synthesis of
benzonitriles. The advantage of this Pd-BNPs is shorter -reaction
time, high yields and easy preparation of Pd-BNPs at room
temperature. Further application of the stable Pd-BNPs as
−161.
R.; Russ. J. Org. Chem. 2010, 46, 157
(19)
(20)
(a) Ganapathy, D.; Sekar, G. Catal. Commun. 2013, 39, 50; (b)
Ganapathy, D.; Sekar, G. Org. Lett., 2014, 16 (15), 3856–3859.
When the reaction was carried out with aryl bromides and aryl
chlorides, there is no any product formation and only starting material
was recovered.
(21)
Typical experimental procedure: Aryliodide (0.5 mmol),
K4[Fe(CN)6].3H2O (0.15 mmol), K3PO4 (1.5 mmol) and Pd-BNP (5.3
mg, 0.005 mmol, 1.0 mol %) were taken in a oven dried reaction tube

4
Tetrahedron Letters
equipped with magnetic pellet. DMF (2.0 mL) was added to the
reaction tube and the reaction mixture was stirred at 120 oC
temperature. The reaction was monitored by TLC. After consumption
of the starting material, the reaction mixture was cooled to room
temperature. Crude product was extracted with ethyl acetate (3 × 10
mL). Then the organic phase was dried over Na2SO4 and concentrated
in vacuum. The product was purified by column chromatography
using silica gel.

Table 1. Screening of bases and solvents for cyanation of aryl iodides using K4[Fe(CN)6]
catalyzed by stable Pd-BNPs.
Entry
1
Base
K2CO3
CS2CO3
KOH
Time(h)
Yield(%)
60
3
3
2
75
3
24
8
10
4
Et3N
20
5
K3PO4
K3PO4
NaOAC
CH3CN
CH3CN:H2O
toluene
Xylene
DMF
3
87
6
8
65b
7
6
35
8
3
87
9
12
24
24
2
trace
trace
trace
92
10
11
12
13
14
15
16
DMAc
Dioxane
DMSO
DMF
24
24
8
82
30
83
24
00c
aIsolated yield; b2.0Equiv. Et3N was used; cWithout Pd-BNPs

Table 2. Pd-BNPs catalyzed cyanation of aryl iodides using K4[Fe(CN)6].
Entry
Aryl halide
product
2a
Time (h)
yield(%)
1
2
92
1a
2
3
2
2
91
87
CN
1b
2b
1c
2c
4
5
2
2
88
90
1d
2d
1e
1f
2e
2f
6
7
8
2
1
1
82
98
90
1g
2g
2h
1h
1i
9
1.5
94
2i

10
2
87
1j
2j
11
12
2
2
88
90
1k
2k
1l
2l
2m
2n
13
14
15
2
2
2
82
98
91
1m
1n
1o
2o
a Isolated yield