Eco-friendly and recyclable media for rapid synthesis of tricyanovinylated aromatics using biocatalyst and deep eutectic solvent

Article abstract of DOI:10.1016/j.catcom.2014.01.031

An efficient and clean synthesis of aromatic tricyanovinyl compounds from nucleophilic reagent and tetracyanoethylene has been achieved using biocatalyst and deep eutectic solvent (DES). Reaction using biocatalyst and DES requires lesser reaction time than conventional method. The advantages of the present method are ambient reaction temperature, easy isolation of the product, higher yield, recyclability of the catalyst, and reactions without use of hazardous, volatile organic solvent. The DES as well as biocatalyst were recycled efficiently without any additional treatment. Synthesized compounds were also studied for UV-vis absorption and show solvatochromism.

Full text of DOI:10.1016/j.catcom.2014.01.031

Catalysis Communications 49 (2014) 58–62
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Eco-friendly and recyclable media for rapid synthesis of
tricyanovinylated aromatics using biocatalyst and deep eutectic solvent
⁎
Anita Kailas Sanap, Ganapati Subray Shankarling
Department of Dyestuff Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai 400019, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and clean synthesis of aromatic tricyanovinyl compounds from nucleophilic reagent and
tetracyanoethylene has been achieved using biocatalyst and deep eutectic solvent (DES). Reaction using biocat-
alyst and DES requires lesser reaction time than conventional method. The advantages of the present method are
ambient reaction temperature, easy isolation of the product, higher yield, recyclability of the catalyst, and reac-
tions without use of hazardous, volatile organic solvent. The DES as well as biocatalyst were recycled efficiently
without any additional treatment. Synthesized compounds were also studied for UV–vis absorption and show
solvatochromism.
Received 31 December 2013
Received in revised form 28 January 2014
Accepted 29 January 2014
Available online 7 February 2014
Keywords:
Tricyanovinylation
Protease enzyme
Deep eutectic solvent
Lipase enzyme
© 2014 Elsevier B.V. All rights reserved.
Solvatochromism
1. Introduction
conditions involving high temperature and volatile organic solvents,
which leads to severe environmental, and ecological problems. Recently,
Organic molecules containing both donor and acceptor moieties are
the focus of intense research because they are critical components for
many advanced technologies such as non-linear optics (NLO) [1],
photo- and electroluminescent devices [2] and photovoltaic devices
[3]. Organic NLO materials have many advantages over inorganic mate-
rials, such as large nonlinear optical co-efficiency, simple preparation
and lower cost [4].
In the last few years, donor substituted tricyanovinylaryl com-
pounds have received lot of interest [5]. It is known that the intro-
duction of cyano groups into an acceptor molecule substantially
enhances its electron acceptor [6] and solvatochromic properties [7].
Tricyanovinylated compounds are of great interest because they possess
a variety of interesting optical properties like, high charge-transfer ability
[8], photosensitizing properties [9] and electrical conductivity [10].
Tricyanovinyl group is about 5–10 times stronger NLO chromophore
than dicyanovinyl unit [11]. Generally, dicyanovinyl compounds can
be converted to the tricyanovinyl analogs by Michael addition of
HCN using sodium cyanide in dimethylformamide [12]. Alternatively,
tricyanovinylaryl compounds can be prepared by the reaction of aryl
amines or N-heterocyclic compounds with tetracyanoethylene (TCNE)
in organic solvents like dimethylformamide, dimethylsulfoxide, diethyl
ether, pyridine and benzene at 60–150 °C to form tricyanovinyl analogs.
All the above methods, however require longer reaction time, drastic
Deligeorgiev et al. reported tricyanovinylation of aromatic amines under
ultrasound irradiation at room temperature or 60 °C in 5–20 min [13].
There is no doubt that this method is greener, but it has limitations re-
garding commercial viability. We have tried to overcome the limitations
and retain the benefits of the reported methods by using biocatalysts or
simple DES as catalyst.
Biocatalysts catalyze many important reactions, including ester hy-
drolysis [14], transesterification [15], enantioselective synthesis [16]
and acylation [17]. Enzymes are also used for performing various assays
that have applications in the area of environmental and food analysis
[18].
The use of environmentally benign solvents like DES represents very
powerful green technology from the synthetic point of view. It not only
reduces the burden of organic solvent disposal, but also enhances the
rate of many organic reactions. DES is similar to conventional ILs in
terms of low vapor pressure and low flammability. In addition, DES
has many advantages over conventional ILs, such as it is biodegradable,
safe, non-toxic, and inexpensive.
In the past few years, our research group has explored applicability
of DES based on choline chloride (ChCl) and biocatalyst in several signif-
icant organic transformations [19,20]. In pursuit of a simple and envi-
ronmentally benign process we herein report a new method for the
synthesis of tricyanovinyl substituted aniline and indole derivatives in
DES and biocatalyst (Scheme 1). The biocatalyst as well as DES could
be recycled without losing its significant activity. The method is simple
and convenient for commercial synthesis.
⁎
Corresponding author. Tel.: +91 22 33612708; fax: +91 22 33611020.
E-mail address: gsshankarling@gmail.com (G.S. Shankarling).
1566-7367/$ – see front matter © 2014 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2014.01.031

A.K. Sanap, G.S. Shankarling / Catalysis Communications 49 (2014) 58–62
59
Scheme 1. Tricyanovinylation of anilines and indoles using DES (ChCl:urea) and biocatalyst.
2. Experimental
2.3. General procedure for tricyanovinylation of N-alkyl anilines and in-
doles in DES
2.1. Materials and equipments
N-substituted aniline or indole (1 mmol) was dissolved in 4 mL DES.
TCNE (1 mmol) was added to the mixture at room temperature and
stirred for appropriate time as shown in Table 1. Hydrogen cyanide
evolved from the reaction was completely scrubbed in a sodium hypo-
chlorite, maintaining pH at around 11 and care was taken to avoid any
leakage by applying mild vacuum to the scrubber. After completion of
the reaction, cold water was added to the reaction mixture. The precip-
itated crystals were filtered off, and purified by FCC using hexane:ethyl
acetate in 9:1 ratio (v/v).
Pure lipase isolated from Pseudomonas sp. and pure protease isolated
from Bacillus subtilis bacteria were used. Both enzymes were purchased
from Roossari Biotech. TCNE was purchased from Aldrich Chemical
Co. 1H NMR and 13C NMR spectra were recorded on Varian 300 MHz
spectrophotometer in CDCl3. Chemical shifts were expressed in δ ppm.
Mass spectral data were obtained with micromass-Q-Tof (YA105)
spectrometer.
2.2. Preparation of DES
2.4. General procedure for tricyanovinylation of N-alkyl anilines and in-
doles in enzyme
The DES was prepared by combining ChCl with urea according to the
procedure reported in the literature [21].
N-substituted aniline or indole (1 mmol), dichloromethane (0.5 mL)
and lipase or protease catalyst (15 wt.% of aniline or indole) was stirred
in a round bottom flask. TCNE (1 mmol) was added to the mixture at
room temperature and stirred for appropriate time as shown in
Table 1. The experimental setup to quench HCN was the same as
given in Section 2.4. After completion of the reaction, the catalyst was
filtered off through a Whatmann-42 filter paper and washed with di-
chloromethane. The filtrate was evaporated on a rotary evaporator
and purified by FCC on silica gel using hexane:ethyl acetate (9:1) to af-
ford pure product.
Table 1
Results of tricyanovinylation reaction in three different conditions.
Entry Starting
material
Productsa
Lipaseb
DESc
Proteased
Yieldf %, t
(min)
Yieldf %, t
(min)
Yieldf %, t
(min)
1
2
3
80, (5)
84, (5)
85, (5)
89, (5)
89, (5)
87, (5)
79, (5)
74, (5)
84, (5)
Table 2
Optimization of catalysts.
4
5
6
70, (10)
75, (7)
78, (5)
74, (10)
84, (5)
87, (5)
68, (10)
74, (7)
75, (5)
Entry
Catalyst
Time (min)
Yielda (%)
1
2
3
4
ChCl:malonic acid
ChCl:oxalic acid
ChCl:urea
25
15
5
70
70
89
80
20
50
40
75
80
10
85
60
68
79
76
66
75
80
80
7
8
83, (10)
75, (12)
80, (10)
82, (12)
79, (10)
73, (15)
Glycerol
30
60
50
60
60
60
60
10
5
5
5
5
5
5
6
7
8
Urea
ChCl
ChCl:ethanol
ChCl:H2O
ChCl:DCM
9e
75, (25)
78, (20)
75, (15)
87, (15)
72, (20)
80, (15)
10
9
10.
11
12
13
14
15
16
17
18
19
ChCl:urea:ethanol
ChCl:urea:DCM
5% Protease
10% Protease
15% Protease
20% Protease
5% Lipase
10% Lipase
15% Lipase
20% Lipase
11
12
76, (15)
80, (15)
81, (15)
85, (10)
75, (15)
80, (15)
5
5
5
aReaction conditions: aniline or indole (1.0 mmol) and tetracyanoethylene (1.0 mmol),
room temperature (35
2 °C). b,d,eIn the reactions, dichloromethane (0.5 mL) was
added. cIn absence of dichloromethane fIsolated yields.
a
Isolated yields.

60
A.K. Sanap, G.S. Shankarling / Catalysis Communications 49 (2014) 58–62
Table 3
ethyl, isobutyl, n-hexyl. Indoles having substitution at 1 and 2 posi-
tions were studied. The reaction was faster in the case of N-alkyl an-
ilines (Table 1, entries 1–7), with excellent yields. The reaction
offered moderate rate even in the case of aryl substituent at nitrogen
of aniline (Table 1, entry 8). It is observed that, N-alkyl anilines are
more reactive towards tricyanovinylation reaction than N-alkyl indoles
(Table 1). Surprisingly, we got better results in both cases than the re-
ported literature.
Recyclability of DES and enzymes in tricyanovinylation of 1a with TCNE.
Entry
Number of runs
Lipase
DES
Protease
Yield(%)
Yield (%)
Yield (%)
1
2
3
4
5
Fresh, non-recycled
First
Second
Third
Fourth
80
82
80
76
70
89
88
86
80
73
79
74
70
66
61
3.3. Recyclability studies
3.3.1. DES recyclability
3. Results and discussion
3.1. Influence of type of catalyst on yield
In view of the need for environmental benign methodologies,
the recovery and reuse of the DES are essential. For recyclability
study, tricyanovinylation of 1a with TCNE was studied as a repre-
sentative reaction. The DES was recovered by filtration of the reac-
tion mass and washing with water. The DES is water soluble while
the product is insoluble. The DES was recovered from the filtrate by
evaporating the water under vacuum. The recycled DES was used
up to four runs without any loss in activity (Table 3).
To recognize the optimization of the reaction conditions, the reac-
tion of N-methyl aniline (1a) with TCNE (2) was studied by employing
various DES and solvents as well as under solvent free conditions with
the hope to maximize the yield (Table 2). The DES obtained from
malonic acid or oxalic acid gave 70% yield of 4a in 25 and 15 min respec-
tively. In glycerol 80% product was formed but reaction time was about
30 min. Surprisingly, ChCl:urea DES provided 89% yield of the desired
product in very short time. Hence, to find out the role of individual
components, the reaction was carried out in the presence of sole
urea. It gave only 20% yield in 60 min and no further improvement
in yield was observed after prolonged reaction time. In the presence
of sole ChCl 50% of the product was formed in 50 min. The role of the
solvent along with the catalyst was found out using ChCl (10 mol%)
as catalyst in various solvents such as ethanol, water and dichloro-
methane (entries 7–9); unfortunately, it gave lower yield of product
as compared to ChCl:urea DES. It indicates that ChCl and urea both
together in deep eutectic form play a vital role in catalyzing the reac-
tion. To prove this, initially we carried out the reaction in ethanol and
dichloromethane with addition of ChCl:urea DES. Ethanol along with
ChCl:urea DES, gave low yield (entry 10) while in the case of dichlo-
romethane, 85% of the product was formed in 10 min (entry 11).
However, the eutectic mixture of ChCl:urea gave best results
amongst all other eutectic mixtures (entry 3). Taking ChCl:urea
DES as the right catalyst for the experiment, we studied the general-
ity of the reaction. On the other hand, the optimization for quantity
of enzyme suggested that 15% (w/w) of enzyme is the optimum
quantity for effective results (entries 12–19).
3.3.2. Enzyme recyclability
Reusability of the enzyme is essential from the economic point of
view. For recyclability study tricyanovinylation of 1a with TCNE was
studied as a representative reaction. Enzyme was recovered by direct
filtration of the reaction mass and with dichloromethane wash. Since
the enzyme is insoluble in dichloromethane it can be easily separat-
ed. The recovered enzyme was used for four successive cycles and
decrease in yield was observed after the third cycle (Table 3).
3.4. Spectral characteristics
The absorption spectra of tricyanovinylaryl compounds (4a–4h
and 5a–5d) were measured in six different solvents having differ-
ent polarities as listed in Table 4 (see supporting information). It
was observed that as the solvent polarity increases, the absorption
wavelength of the compounds also increases. The absorption max-
ima showed a red shift with the increase in the solvent polarity
which extended from 448 nm to 538 nm. All dyes exhibited intense
color in day light. Fig. 1 displays the photograph of 4b in daylight
taken in various solvents. A number of the compounds have not
been previously reported, specifically 4d, 4e, 4f, 5b, 5c and 5d.
These were fully characterized by 1H NMR, 13C NMR and mass anal-
yses (see supporting information).
3.2. Ttricyanovinylation reaction of anilines or indoles
with tetracyanoethylene
3.5. Proposed mechanism
To study the scope and limitations of this protocol, we employed
a wide range of anilines and indoles. The anilines include substitu-
tion at nitrogen and consisted of various alkyl groups such as methyl,
Although the role of DES and biocatalyst in the present work is yet to
be confirmed, we suggest the following mechanism. In DES catalyzed
Fig. 1. Photograph of 4b in daylight taken in various solvents.

A.K. Sanap, G.S. Shankarling / Catalysis Communications 49 (2014) 58–62
61
R1 R2
N
R1
R2
H3C
H3C
H3C
O
H
N
N
Cl
O
H
H
NC
H
N
H
N
H
N
CN
CN
CN
N C
CN
NC
Hydrogen bonding
interaction responsible TCNE due to hydrogen
for formation of DES bonding with DES
Increase in reactivity of
CN
R1
R2
R1
R2
N
N
-HCN
NC
NC
CN
H
CN
CN
NC
CN
Tricyanovinylated
aniline derivative
Rearomatization of aniline
Scheme 2. Mechanism proposing the role of DES in synthesis of tricyanovinyl derivatives.
R1
R2
R2
R1
R2
R1
N
N
N
H
N
H
H
H
O
O
N
H
H
C
CN
CN
H
H
H
CN
NC
Asp
His
CN
H
H
N
NC
NC
NC
NC
H
N
CN
Rearomatization of aniline by His residue
O
O
O
O
R1
R2
Asp
His
N
Asp
His
H
HCN
H
N
N
N
H
N
CN
CN
CN
NC
Tricyanovinylated
aniline derivative
Regeneration of His-Asp dyad
and evolution of HCN gas
Cyanide ion abstracts hydrogen
from protonated His-residue
Scheme 3. Mechanism proposing the role of enzyme in synthesis of tricyanovinyl derivatives.
mechanism, urea forms hydrogen bonding with ChCl. Similarly, it
also forms hydrogen bond with nitrogen of TCNE and increases its
electrophilicity, thereby facilitating the attack of activated aromatic
ring. Finally, a proton of the aromatic ring gets abstracted by a cya-
nide ion and is released as HCN gas (Scheme 2).
and regeneration of Asp-His dyad takes place with evolution of HCN
gas (Scheme 3).
4. Conclusion
In enzyme catalyzed mechanism, firstly, TCNE is pre-activated by
the enzyme. Lipase and protease are also known to function by
means of proton abstraction by Asp-His dyad [22,23]. Then, in the
second step, a proton was transferred from the aromatic ring to the
His residue and the desired product is obtained via aromatization.
Finally, cyanide ion abstracts proton from the protonated His residue
Herein, we report a simple, green and efficient catalytic protocol
for the preparation of various aromatic tricyanovinyl compounds
using biocatalyst or DES. The reaction gave excellent yields at room
temperature in very short time. The present method eliminates the
need of hazardous organic solvents and expensive catalysts. The
highlights of the catalyst include its bio-degradability, non-toxic

62
A.K. Sanap, G.S. Shankarling / Catalysis Communications 49 (2014) 58–62
nature, ease in preparation and requirement of inexpensive starting
materials. The catalyst was also easily recyclable with no loss in yields at
least up to four runs.
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Appendix A. Supplementary data
Supplementary data to this article can be found online at http://dx.
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