Oxidative cyanide-free cyanation on arylboronic acid derivatives using aryl/heteroaryl thiocyanate using novel IL-PdCl4 catalyst under mild condition

Article abstract of DOI:10.1080/17415993.2018.1469632

An efficient and simple method is reported for the cyanation on arylboronic acid using various simple/indole thiocyanates using a new IL-PdCl₄ catalyst. The cascade process involves a coupling reaction without any additive to give a wide range of cyanide derivatives. Cyanation on various arylboronic acids underwent smoothly affording the corresponding arylnitriles in good to high yields.

Full text of DOI:10.1080/17415993.2018.1469632

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Oxidative cyanide-free cyanation on arylboronic
acid derivatives using aryl/heteroaryl thiocyanate
using novel IL-PdCl catalyst under mild condition
4
Beena K. Vaghasiya, Shailesh P. Satasia, Rahul P. Thummar, Ronak D.
Kamani, Jemin R. Avalani, Nirav H. Sapariya & Dipak K. Raval
To cite this article: Beena K. Vaghasiya, Shailesh P. Satasia, Rahul P. Thummar, Ronak D.
Kamani, Jemin R. Avalani, Nirav H. Sapariya & Dipak K. Raval (2018): Oxidative cyanide-free
cyanation on arylboronic acid derivatives using aryl/heteroaryl thiocyanate using novel IL-PdCl4
catalyst under mild condition, Journal of Sulfur Chemistry, DOI: 10.1080/17415993.2018.1469632
To link to this article: https://doi.org/10.1080/17415993.2018.1469632
Published online: 09 May 2018.
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JOURNAL OF SULFUR CHEMISTRY, 2018
https://doi.org/10.1080/17415993.2018.1469632
Oxidative cyanide-free cyanation on arylboronic acid
derivatives using aryl/heteroaryl thiocyanate using novel
IL-PdCl catalyst under mild condition
4
a
a
a
a
Beena K. Vaghasiya , Shailesh P. Satasia , Rahul P. Thummar , Ronak D. Kamani ,
b
c
a
Jemin R. Avalani , Nirav H. Sapariya and Dipak K. Raval
a
b
Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar, Gujarat, India; Shree A. N. Patel P. G.
c
Institute of Science and Research, Anand, Gujarat, India; Natubhai V. Patel College of Pure and Applied
Sciences, Vallabh Vidyanagar, Gujarat, India
ABSTRACT
ARTICLE HISTORY
An efficient and simple method is reported for the cyanation on aryl-
boronic acid using various simple/indole thiocyanates using a new
IL-PdCl4 catalyst. The cascade process involves a coupling reaction
without any additive to give a wide range of cyanide derivatives. Cya-
nation on various arylboronic acids underwent smoothly affording
the corresponding arylnitriles in good to high yields.
Received 30 November 2017
Accepted 21 April 2018
KEYWORDS
Thiocyanation; IL-PdCl4;
FE-SEM; arylboronic acid;
indoline derivatives
1. Introduction
Aryl nitriles are important from the view point of a number of drugs [1–3]. They have
emerged as basic constituents of dyes and herbicides [4]. They can be transformed into
CONTACT Beena K. Vaghasiya
beenapatel2808@gmail.com, dipanalka@yahoo.com
Department of Chemistry,
Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, India
Supplemental data for this article can be accessed here. https://doi.org/10.1080/17415993.2018.1469632
2018 Informa UK Limited, trading as Taylor & Francis Group
©

2
B. K. VAGHASIYA ET AL.
various compounds such as carboxylic acids, amides, amines, imines, aldehydes and tetra-
zoles because of tunable reactivity of the cyano group [5]. Conventional cyanation methods
for the synthesis of nitrile compounds typically employ corresponding organic halides or
diazonium salts with copper cyanide [6,7] or the combination of cyanide anion equivalents
and transition-metal catalysts [8–12]. Among various available methods, the Sandmeyer
and Rosenmund-von Braun reactions have been widely used in aromatic cyanation [13,14].
Many direct cyanation reactions have been reported by metal cyanide (MCN), such as
KCN, NaCN, CuCN, Zn(CN) , AgCN and TMSCN. [15,16]. High toxicity is a serious
2
issue common with all of them. The transition metal-mediated cyanation reactions have
been more attractive during these years. Palladium and copper metals are most commonly
involved in these reactions [17–20]. The reaction usually proceeds at high temperature
with prolonged times. Due to the drawbacks of cyanation using such toxic cyanide sources,
many groups have focused on developing cyanide free cyanation by using non-toxic
cyanide source like dimethylformamide (DMF) [21]. More recently, cyanation of aryl
halides has been developed as a useful alternative for the preparation of aryl nitriles [22,23].
Arylboronic acid derivatives are readily available and easy to handle coupling partners in
transition metal catalyzed coupling reactions [24–27]. Much attention has been paid to the
direct catalytic oxidative cyanation of arylboronic acid derivatives as a method to access
aromatic nitriles.
However, to the best of our knowledge, there are only a few examples regarding the
transformation of arylboronic acids into aryl nitriles, which used transition-metal catalysts
[
11, 28–30]. Some of them need additives or Cu source. In our present report only catalyst
is successfully attempted for the purpose. Enlightened by the fact that thiocyanate could
work as a cyanide anion surrogate for the palladium catalyzed cyanation of arylboronic
acids [31], we envisaged that the combination of thiocyanate with a palladium catalyst
might lead to the development of a practical method for the cyanation of arylboronic acids
without the need of any additives. The protocol was well optimized with different reaction
parameters and successfully applied to a variety of arylboronic acids.
Table 1. Optimization of the reaction conditions for preparation
of 4b using IL-PdCl4.
Entrya
Pd (mol %)
Solvent
Temp.(°C)
Yield (%)b
1
2
3
4
5
6
7
8
9
-
THF
DMSO
Toluene
DMF
EtOH
CHCl3
PEG
THF
THF
THF
THF
180
110
Reflux
180
Reflux
180
180
180
Reflux
rt
38
20
12
45
trace
45
56
trace
41
90
90
0.5
0.5
0.5
0.5
0.5
0.5
0.1
0.3
0.5
1.5
2.0
10
11
12
rt
rt
THF
90
aReactions were performed using 1-amino-4-thiocyanatobenzene (1 mmol),
-methoxy-3-methyl phenylboronic acid (2 mmol.), 20% aq. Na2CO3 (1 mL)
4
and Xylene (4 mL), IL-PdCl4 in various solvents (2 ml) for a reaction.
b
Isolated yield.

JOURNAL OF SULFUR CHEMISTRY
3
2. Results and discussion
The control experiment without catalyst gave the corresponding product in a rather low
yield of 38%, which indicated that the catalyst played an important role in the reaction
(
Table 1, Entry 1). Effect of other solvents and reaction temperature were also investigated
up to 12 h but lower yields of the products were reported (Table 1, Entries 2–9). Loading
of 0.5 mol% of the IL-PdCl catalyst using THF as co-solvent at room temperature showed
4
great efficiency for the reaction within 2.5 h (Table 1, Entry 10). The desired product was
obtained in nearly quantitative yield. Further increase in the amount of catalyst does not
affect the percentage of yield (Table 1, Entries 11–12). Finally, the most suitable reaction
condition for the model reaction was chosen as: substituted phenylboronic acid (2 mmol),
aryl/heteroaryl thiocyanate (1 mmol) in the presence of 20% aqueous Na CO (1 mL),
2
3
Table 2. IL-PdCl4 catalyzed cyanation on arylboronic acid using (2a-f)/(3a-d)a
.
2
a-f
3a-d
Entrya
Product
R
R1
Time (h)b
Yield (%)c
R2
-H
2-Me
5-NO2
5-Br
5-Br
5-Br
5-Br
5-NO2
2-Me
5-NO2
2-Me
5-NO2
5-NO2
5-Br
Time (h)b
Yield (%)c
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
-H
4-Br
2.0
2.5
2.0
2.5
2.5
2.0
2.5
2.5
2.5
2.5
2.0
2.0
3.0
2.0
2.0
95
90
91
86
90
87
89
93
91
94
92
94
91
87
89
2.0
2.5
2.0
2.5
2.0
2.5
2.0
2.5
3.0
2.0
2.5
2.5
2.0
2.0
2.5
93
91
90
87
90
89
86
86
90
91
90
90
92
87
90
3-Me, 4-OMe
4-OMe
2,3-F
Pyridine
2-F,4-OMe
3-NO2
4-NH2
4-Cl
4-NH-Et
4-NH2
4-Cl
4-Cl
4-NO2
4-NH2
1-NH-Me
2-CH3,6-NH2
4-NH-Me
4-Cl
4-NH2
4-NH2
4-Cl
3-CHO
4-CHO
4-Br
10
11
12
13
14
15
4-CN
3-CH2OH
3-CF3
4-OBn
5-Br
aReactions performed using aryl derivatives 2a-f/indole derivatives 3a-d (1 mmol.), arylboronic acid (2 mmol.), 20%
aq.Na2CO3 (1 mL), Xylene (4 mL), THF (2 mL), catalyst IL-PdCl4 (0.5 mol%).
b
All the reactions were run till completion as indicated by TLC.
c
1
Isolated yields. All synthesis compounds are confirmed by H NMR.

4
B. K. VAGHASIYA ET AL.
THF as co-solvent and xylene (4 mL) using 0.5 mol% of the IL-PdCl catalyst should be
4
allowed to react at room temperature for 2.5 h.
Initially, we attempted the cyanation on phenylboronicacid (1a) using 1-bromo-4-
thiocyanatobenzene (2a)/1H-indole (3a) in the presence of IL-PdCl (0.5 mol%) as catalyst
4
and base 20% aqueous Na CO (1 mL) and Xylene (4 mL) in 2 ml THF to give 4a within 2 h
2
3
of reaction time (Table 2, Entry 1). Phenylboronic acid bearing either electron-donating or
electron-withdrawing substituents afforded the corresponding products in good to excel-
lent yields. The use of substituted thiocyanto-1H-indole in cyanation on arylboronic acid
also underwent smoothly. Both aryl thiocyanate and indole thiocyanate gave good yield
for the corresponding products (Table 2, Entries 2–15).
In the reaction leading to the formation of 4a using 3a the by-product was characterized
as 3 -indolylthiol by mass spectral analysis. As our interest was to focus only on cyanation
that can be achieved by avoiding hazardous cyanide source using thiocyanato derivatives,
the by-product formation is not reported in this study.
In our study, the catalyst IL-PdCl showed a much higher activity in terms of short
4
reaction time, milder reaction conditions and lower cost in comparison with the other cat-
alysts employed for the synthesis of aryl cyanide derivatives. Any expensive ligands and/or
oxidants were not required to give excellent yield as shown in Table 3.
The reusability of catalysts is an important factor for commercial uses. The reusability of
the catalyst was also examined in the synthesis of 4b (4-methoxy-3-methylbenzonitrile).
The catalyst was easily recovered after each run from the reaction medium. It was washed
with acetonitrile dried under vacuum at 120°C and tested for its activity in subsequent
a
Table 3. Catalysis screening study of the present protocol over some reported catalysts
Entry
Catalyst
Ligand/oxidant
Yield (%)b
Ref.
1
2
3
4
5
7
8
9
a
Pd(pph3)4
Pd(OAc)2
(CuOTf)2/CuF
{Rh(OH)(Cod)}2
CuI/TBHP
PdCl2(dppe)
Pd(OAc)2/K4[Fe(CN)6] 3 H2O
IL-PdCl4
CuTc/O2
Xantphose/O2
dtbpy
K2CO3/Air
–
HCOONa
CM-phose
–
90
82
76
70
87
76
93
95
[11]
[32]
[26]
[29
[30]
[27]
[33]
a
Present work
Phenylboronic acid (2 .0 mmol) and 1 -bromo-4 -thiocyanatobenzene(1 .0 mmol) at room temperature
27 ± 1 C).
0
(
b
Isolated yield.
Table 4. StudyonreusabilityofIL-PdCl4 inthereactiona.
b
Entry
Cycle
Yield (%)
1
2
3
4
a
First (fresh run)
Second cycle
Third cycle
94
92
88
88
Fourth cycle
Reaction was run with 4-thiocyanatoaniline (2c, 1 mmol), 4-
methoxy-3-methyl Phenyl Boronic acid (1c, 2 mmol), 20% Na2CO3
(
1 mL), Xylene(4 mL)andcatalystIL-PdCl4 (0.5 mol%)inTHF(2 mL).
Isolated yield.
Reactions were run till completion as indicated by TLC.
b
c

JOURNAL OF SULFUR CHEMISTRY
5
runs. It was found that the catalyst could be reused for four times without much loss of
activity (Table 4, Entries 1–4).
3. Conclusion
We have developed a new palladium catalyst IL-PdCl protocol for the generation of a
4
cyano functionalization on arylboronic acid from aryl/heteroaryl thiocyanato derivatives
under very mild reaction conditions. This methodology is applicable in synthesizing a wide
range of nitriles derivatives without any use of hazardous cyanide material.
4. Experimental section
4.1. Materials and instrumentation
All the reactions were carried out with commercially available reagents. They were used
without further purification. Organic solvents were purified by standard methods [29].
All the reactions were monitored by TLC on fluorescent coated plates (aluminum plates
coated with silica gel 60 F254, 0.25 mm thickness, Merck) and detection of the compo-
nents was made by exposure to UV light. Melting points were measured in μThermoCal10
(
Analab Scientific Pvt Ltd., India) and the reported values are uncorrected. The synthe-
1
sized compounds were identified by H NMR spectra recorded using DMSO-d as well
6
as CDCl as solvents on BrukerAvance 400 MHz spectrometer (Bruker Scientific Cor-
3
poration Ltd., Switzerland). The chemical shifts are reported in δ ppm. IR spectra were
−
1
recorded on Bruker alpha E-FT-IR spectrophotometer over the range 4000–400 cm and
frequencies of only characteristic peaks are expressed. Elemental analyses were performed
on Perkin Elmer 2400 series-II Elemental Analyser (Perkine Elmer, USA) and all results are
found within ± 0.4% of the theoretical compositions. Field Emission-Scanning Electron
Microscopy (FE-SEM) analysis was performed on Hitachi-PU (SU8000) instrument.
4
.2. General procedure for the synthesis of IL-Pdcl4
To the aqueous solution of N,N,N-trimethyl-2-(sulfooxy)ethanaminium chloride[10]
1.48 g, 2 mmol, 2eq.), anhydrous sodium tetrachloropalladate(ll) (1.0 g, 1 mmol, 1eq.) was
(
added under vigorous stirring. Five milliliters of isopropyl alcohol was then added drop
wise and stirring was continued for 4–5 h at room temperature. After completion of the
reaction, the mixture was filtered, obtained solid was washed with six successive aliquots
of 5 mL acetonitrile and dried at room temperature to afford N,N,N-trimethyl-2-(sulfooxy)
ethanaminium palladium(II) chloride (IL-PdCl ) (Scheme 1).
4
Scheme 1. Synthesis of IL-PdCl4 catalyst.

6
B. K. VAGHASIYA ET AL.
Figure 1. FT-IR spectrum of IL-PdCl4.
Figure 2. FE-SEM analysis of IL-PdCl4 with different milling time.
4
.3. FT-IR analysis of IL-PdCl4
The FT-IR spectrum of IL-PdCl catalyst is shown in Figure 1. In the IR spectra, S = O
4
−
1
stretching vibrations appeared at 1149 and 1224 cm to confirm the presence of −SO H
3

JOURNAL OF SULFUR CHEMISTRY
7
Figure 3. EDX analysis of IL-PdCl4.
groups in the catalyst. It also exhibited two featured bands at 1442 and 1381 cm−1 which
can be assigned to the stretching vibration of the C–C bond and the bending vibration of
−
1
the C–H bond, respectively, while N–H bending vibration was observed at 1604 cm and
−1
N–H stretching vibration at 3454 cm
.
4.4. FE-SEM and EDX analysis of IL-PdCl4
The morphological characteristics developed for the synthesized IL-PdCl catalyst was
4
observed under FE-SEM as shown in Figure 2. Morphology of the composite displays a
homogeneous structure. Roughly spherical morphology was visualized in Figure 2(c,d).
The Energy Dispersive X-ray (EDX) analysis of IL-PdCl catalyst is shown in Figure 3.
4
The strong peak observed at 3.2 keV indicated the presence of Pd element. Other existing
elements as revealed by the EDX analysis were carbon, oxygen, and chlorine and are in
agreement with calculated observation.
Acknowledgements
Authors are thankful to SAIF analysis, for FE-SEM analysis, Chandigarh. The authors are thankful
to the Head, Department of Chemistry, Sardar Patel University for providing research facilities.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
BKV and RPT wish to acknowledge the University Grants Commission, New Delhi, India for mer-
itorious fellowship. NHS acknowledges the University Grants Commission, New Delhi, India for
UGC-JRF.

8
B. K. VAGHASIYA ET AL.
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