CeCl3·7H2O catalyzed C(sp2)?CN bond construction on water: Synthesis of (Z)-2-(2-Oxoindolin-3-ylidene)-2-arylacetonitriles

Article abstract of DOI:10.1080/00397911.2018.1540050

An environmentally friendly method for the construction of C(sp²)–CN bond on water has been described, and (Z)-2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles were synthesized by using CeCl₃· 7H₂O as a catalyst. The reactio

Full text of DOI:10.1080/00397911.2018.1540050

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
CeCl3·7H2O catalyzed C(sp2)−CN bond construction
on water: Synthesis of (Z)-2-(2-Oxoindolin-3-
ylidene)-2-arylacetonitriles
Yan Du & Zheng Li
To cite this article: Yan Du & Zheng Li (2019): CeCl3·7H2O catalyzed C(sp2)−CN bond
construction on water: Synthesis of (Z)-2-(2-Oxoindolin-3-ylidene)-2-arylacetonitriles, Synthetic
Communications, DOI: 10.1080/00397911.2018.1540050
To link to this article: https://doi.org/10.1080/00397911.2018.1540050
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SYNTHETIC COMMUNICATIONSV
https://doi.org/10.1080/00397911.2018.1540050
CeCl3Á7H2O catalyzed C(sp2)ÀCN bond construction on
water: Synthesis of (Z)-2-(2-Oxoindolin-3-ylidene)-2-
arylacetonitriles
Yan Du and Zheng Li
College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu,
P.R. China.
ABSTRACT
ARTICLE HISTORY
Received 31 August 2018
An environmentally friendly method for the construction of
C(sp2)–CN bond on water has been described, and (Z)-2-(2-oxoindo-
lin-3-ylidene)-2-arylacetonitriles were synthesized by using CeCl3Á
7H2O as a catalyst. The reaction offers access to alkenyl nitriles in
good-to-excellent yield. The investigations will be beneficial to
reduce the use of toxic organic solvents and explore the efficient
catalytic processes on water.
KEYWORDS
CeCl3Á7H2O; on water; (Z)-
2-(2-oxoindolin-3-ylidene)-2-
arylacetonitrile
GRAPHICAL ABSTRACT
Introduction
Alkenyl nitriles are core structure motifs in natural products and pharmaceuticals
(Fig. 1).[1] In addition, alkenyl nitriles also serve as precursors for a range of building
blocks, such as amides, amidines, ketones, and heterocycles.[2] The reported typical syn-
thetic methods for alkenyl nitriles include (i) the palladium-catalyzed cyanation of
alkenyl halides;[3] (ii) the nickel-catalyzed carbocyanation of alkynes;[4] (iii) the ruthe-
nium-catalyzed a-olefination of nitriles;[5] and (iv) the direct cyanation of indoles.[6]
However, these methods use expensive catalysts, toxic solvents, and complex ligands.
Therefore, it is of great importance to explore an easy and environmentally friendly way
to synthesize alkenyl nitriles.
Ã
CONTACT Zheng Li
University, Lanzhou, Gansu 730070, P.R. China.
lizheng@nwnu.edu.cn
College of Chemistry and Chemical Engineering, Northwest Normal
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
Y. DU AND Z. LI
Figure 1. Representative examples bearing alkenyl nitrile structures.
It is widely acknowledged that water serves as an important medium for all chemical
reactions of life.[7] However, it was not applied to organic chemistry until early 1980s.
Breslow found that water could promote the rate of some reactions which had made it
possible for water to become solvent in organic reaction.[8] In contrast to classical trad-
itional organic solvents that have the disadvantages of poisonous and difficult to handle,
water has the obvious advantage of environmentally friendly, economic, and polar
nature. Recently, “on-water” reactions have become one of the most potential areas of
research in green chemistry.[9] Meanwhile, CeCl3.7H2O has been demonstrated to be as
a mild water-tolerable Lewis acid and green catalyst since the earlier introduction of
CeCl3Á7H2O by Luche.[10] Compared with traditional Lewis acid catalyst limited by
strict anhydrous conditions, CeCl3.7H2O outperforms on water and it serves as the
most attractive Lewis acidic catalyst in organic synthesis.[11]
As an extension of our investigation on the various methods for the synthesis of
compounds including cyano group,[12] herein, we report an environmentally friendly
and efficient method for the synthesis of (Z)-2-(2-oxoindolin-3-ylidene)-2-arylacetoni-
triles through C(sp2)–CN bond construction on water by using CeCl3Á7H2O as
a catalyst.
Results and discussion
Initially, the reaction of (E)-3-benzylideneindolin-2-one (1a) with trimethylsilyl cyanide
(TMSCN) was selected as the model reaction to screen the optimal conditions, which
included the use of different catalysts, bases, and solvents at a certain temperature for

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Table 1. Optimization of the reaction conditionsa.
.
Entry
Catalyst
None
NiCl2
FeCl3
InCl3
Base
KOH
KOH
KOH
KOH
Solvent
Yield [%]b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
DMF
DMSO
THF
20
0
0
41
93
25
35
16
trace
0
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
CeCl3Á7H2O
KOH
NaHCO3
K2CO3
Cs2CO3
t-BuOK
DBU
DABCO
Et3N
KOH
KOH
KOH
KOH
0
0
58
52
trace
30
23
73
PhMe
EtOH
MeCN
KOH
KOH
aReaction conditions: 1a (1 mmol), TMSCN (1.2 mmol), catalyst (0.1 mmol), and base (1 mmol) in solvent (5 mL) were
refluxed for 2 h.
bIsolated yield.
an appropriate time. The results are summarized in Table 1. It was found that the reac-
tion readily proceeded on water using KOH as a base leading to produce (Z)-2-(2-
oxoindolin-3-ylidene)-2-phenylacetonitrile (2a) in 20% yield (Table 1, entry 1). This
result prompted us to further search for the optimal reaction conditions. Addition of
10 mol % of NiCl2, FeCl3, InCl3, and CeCl3Á7H2O as catalysts was tested (Table 1,
entries 2 À 5). CeCl3Á7H2O exhibited the best catalytic effect and gave the highest yield
(93%) (entry 5). Some other bases, such as NaHCO3, K2CO3, Cs2CO3, t-BuOK, DBU,
DABCO, and Et3N, were also tested for the reaction (entries 6 À 12). No improved yield
of 2a was observed. In addition, in our investigation of the organic solvents, such as
DMF, DMSO, THF, PhMe, EtOH, and MeCN (Table 1, entries 13 À 18), it was found
that the reaction in these solvents could not give higher yield of 2a than the reaction
on water.
By using the optimized conditions, synthesis of (Z)-2-(2-oxoindolin-3-ylidene)-2-ary-
lacetonitriles was conducted by reactions of various (E)-3-arylideneindolin-2-ones with
TMSCN catalyzed by CeCl3Á7H2O in the presence of KOH at reflux on water. The
results are shown in Table 2. The reactions worked well for a wide range of substrates
bearing both electron-donating (Me, MeO) and electron-withdrawing groups (F, Cl, Br,
NO2, and CF3) on their aromatic rings, and afforded the desired products in good-to-
excellent yields (2bÀ2r). Meantime, the substrates including fused aromatic ring (naph-
thalene), heterocycle (thiophene), and disubstituted aromatic rings also afforded the

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Y. DU AND Z. LI
Table 2. Scope of Ar rings of 1 for the synthesis of 2a.
aReaction conditions: 1 (1 mmol), TMSCN (1.2 mmol), CeCl3Á7H2O (0.1 mmol), and KOH (1 mmol) in H2O
(5 mL) was refluxed for 2 h.

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corresponding products in satisfactory yield (2sÀ2w). In addition, different scope of
2-oxoindoline rings was also tested. Representative alkenyl nitriles 3aÀ3e could be
achieved in good yield for all the tested cases ( Table 3).
In order to gain insight into the reaction pathway, control experiments were per-
formed ( Scheme 1). Under N2 atmosphere, the reaction of 1a with TMSCN was
attempted and only Michael addition product 4a could be observed in 32% of yield.
However, the further reaction of 4a using the standard condition under air atmosphere
Table 3. Scope of 2-oxoindoline rings of 1 for the synthesis of 3a.
aReaction conditions: 1 (1 mmol), TMSCN (1.2 mmol), CeCl3Á7H2O (0.1 mmol), and KOH (1 mmol) in H2O (5 mL) was
refluxed for 2 h.
Scheme 1. Control experiments.

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Y. DU AND Z. LI
Scheme 2. Proposed mechanism for 2a.
could produce 2a in 99% yield. This result indicated that 4a may be the intermediate of
the reaction of 1a with TMSCN to afford 2a.
On the basis of the above results, a plausible mechanism is proposed for the synthesis
of 2a ( Scheme 2). Firstly, 1a was combined with CeCl3 to form a complex A. A was
attacked by cyanide from TMSCN in the presence of KOH to form an intermediate B.
B released CeCl3 to afford Michael addition product 4a. Then, C–H hydroxylation of 4a
is promoted by KOH using atmospheric air as an oxidant to afford intermediate C. The
similar reactions were also reported by Gnanaprakasam and coworkers.[13] Finally,
intermediate C underwent dehydration to give 2a as a final product.
Conclusions
In summary, a method for synthesis of (Z)-2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles
on water catalyzed by CeCl3Á7H2O has been developed. The salient features of this
protocol include high yield, high substrate adaptability, cheap and green catalyst, and
environmentally friendly solvent. This method is a rare example of a reaction model of
C(sp2)ÀCN bond construction on water and conform to the green chemistry develop-
ment and might be provide a better alternative to the synthesis of alkenyl nitriles.
Experimental
1H NMR and 13C NMR spectra were recorded on a Mercury-600MB instrument
(Varian, USA) using CDCl3 and DMSO-d6 as solvents and Me4Si as an internal stand-
ard. Elemental analyses were performed on a Vario El Elemental Analysis instrument
(Elementar, Germany) . Melting points were observed in an electrothermal melting
point apparatus. 3-Arylideneindolin-2-ones (1) were synthesized according to litera-
ture method.[14]

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Typical experimental procedure for the synthesis of (Z)-2-(2-oxoindolin-3-ylidene)-
2-arylacetonitriles
The mixture of (E)-3-arylideneindolin-2-ones (1 mmol), TMSCN (1.2 mmol), KOH
(1 mmol), CeCl3Á7H2O (0.1 mmol), and water (5 mL) was stirred at 100 ꢀC for 2 h. The
reaction was monitored by TLC. After the completion of the reaction, the solid was fil-
tered and washed with 15 mL of water, and recrystallized from EtOAc to afford the
pure products.
Funding
The authors thank the National Natural Science Foundation of China (21462038) for the financial
support of this work.
References
[1] (a) Dalisay, D. S.; Molinski, T. F. Structure Elucidation at the Nanomole Scale. 2. Hemi-
Phorboxazole A from Phorbas sp. Org. Lett. 2009, 11, 1967–1970; (b) Kato, Y.; Fusetani,
N.; Matsunaga, S.; Hashimoto, K.; Fujita, S.; Furuya, T. Bioactive Marine Metabolites. Part
16. Calyculin A. A Novel Antitumor Metabolite from the Marine Sponge Discodermia
Calyx. J. Am. Chem. Soc. 1986, 108, 2780–2781; (c) Zhang, J.; Xu, C. Y.; Wu, W.; Cao, S.
Mild and Copper-Free Stereoselective Cyanation of gem-Difluoroalkenes by Using Benzyl
Nitrile as a Cyanating Reagent. Chemistry. 2016, 22, 9902–9908; (d) Pradal, A.; Evano, G.
A Vinylic Rosenmund-Von Braun Reaction: Practical Synthesis of Acrylonitriles. Chem.
Commun. (Camb.) 2014, 50, 11907–11910. doi:10.1021/ol9004189
[2] (a) Rappoport, Z. The Chemistry of the Cyano Group; Interscience Publishers, London,
1970. (b) Larock, R. C. Comprehensive Organic Transformations: A Guide to Functional
Group Preparations; VCH, Weinheim, 1989.
[3] Powell, K. J.; Han, L. C.; Sharma, P.; Moses, J. E. Chemoselective Palladium-Catalyzed
Cyanation of Alkenyl Halides. Org. Lett. 2014, 16, 2158–2161. doi:10.1021/ol500618w
[4] Nakao, Y.; Yada, A.; Ebata, S.; Hiyama, T. J. A Dramatic Effect of Lewis-Acid Catalysts on
Nickel-Catalyzed Carbocyanation of Alkynes. J. Am. Chem. Soc. 2007, 129, 2428–2429.
doi:10.1021/ja067364x
[5] Thiyagarajan, S.; Gunanathan, C. Ruthenium-Catalyzed a-Olefination of Nitriles Using
Secondary Alcohols. Acs Catal. 2018, 8, 2473–2478. doi:10.1021/acscatal.7b04013
[6] Yan, G.; Kuang, C.; Zhang, Y.; Wang, J. Palladium-Catalyzed Direct Cyanation of Indoles
with K 4 [Fe(CN) 6 ]. Org. Lett. 2010, 12, 1052–1055. doi:10.1021/ol1000439
[7] (a) Ludwig, R. Water: From Clusters to the Bulk. Angew. Chem. Int. Ed. Engl. 2001, 40,
1808–1827; (b) Ball, P. Water as a Biomolecule. Chemphyschem 2008, 9, 2677–2685. doi:
10.1002/1521-3773(20010518)40:10<1808::AID-ANIE1808>3.0.CO;2-1
[8] (a) Breslow, R. Hydrophobic Effects on Simple Organic Reactions in Water. Acc. Chem.
Res. 1991, 24, 159–164; (b) Breslow, R. Determining the Geometries of Transition States
by Use of Antihydrophobic Additives in Water. Acc. Chem. Res. 2004, 37, 471–478. doi:
10.1021/ar00006a001
[9] (a) Chanda, A.; Fokin, V. V. Organic Synthesis “on water”. Chem. Rev. 2009, 109,
725–748; (b) Butler, N.; Coyne, A. G. Chem. Rev. 2010, 110, 6302–6337. doi:10.1021/
cr800448q
[10] Luche, J. L. Lanthanides in Organic Chemistry. 1. Selective 1,2 Reductions of Conjugated
Ketones. J. Am. Chem. Soc. 1978, 100, 2226–2227.
[11] (a) Bartoli, G.; Marcantoni, E.; Marcolini, M.; Sambri, L. Applications of CeCl(3) as an
Environmental Friendly Promoter in Organic Chemistry. Chem. Rev. 2010, 110,
6104–6143; (b) Bartoli, G.; Bosco, M.; Giuli, S.; Giuliani, A.; Lucarelli, L.; Marcantoni, E.;

8
Y. DU AND Z. LI
Sambri, L.; Torregiani, E. Efficient Preparation of 2-Indolyl-1-Nitroalkane Derivatives
Employing Nitroalkenes as Versatile Michael Acceptors: New Practical Linear Approach
to Alkyl 9 H -b-Carboline-4-Carboxylate. J. Org. Chem. 2005, 70, 1941–1944. doi:10.1021/
cr100084g
[12] (a) Song, G.; Li, Z. One-Pot Multi-Component Synthesis of Triarylacrylonitriles Directly
by Using CaC 2 as a Concise Acetylene Source and K 4 [Fe(CN) 6 ] as an Eco-Friendly
Cyanide Source. Eur. J. Org. Chem. 2018, 2018, 1326–1332; (b) Li, Z.; Wen, F.; Yang, J.
Selective Monohydrocyanation of Diimine Using Potassium Hexacyanoferrate(II)-Benzoyl
Chloride Reagent System as a Cyanide Source. J. Chem. Sci. 2016, 128, 1849–1853; (c) Xie,
D. M.; Li, Z. Synthesis of 2-(2-Oxoindolin-3-Ylidene)-2-Arylacetonitriles through
Transition Metal-Free C(sp 2 ) CN Bond Construction. Tetrahedron 2018, 74, 1135–1143;
(d) Li, Z.; Yin, J. Conjugate Hydrocyanation of Chalcone Derivatives Using Ethyl
Cyanoacetate as an Organic Cyanide Source. Chin. J. Chem. 2017, 35, 1179–1184. doi:
10.1002/ejoc.201701711
[13] Chaudhari, M. B.; Sutar, Y.; Malpathak, S.; Hazra, A.; Gnanaprakasam, B. Transition-
Metal-Free C–H Hydroxylation of Carbonyl Compounds. Org. Lett. 2017, 19, 3628–3631
[14] Barakat, A.; Al-Majid, A. M.; Islam, M. S.; Ali, M.; Soliman, S. M.; Siddiqui, M. R. H.;
Ghabbour, H. A.; Fun, H. K. Molecular Structure Investigation and Tautomerism Aspects
of (E)-3-Benzylideneindolin-2-One. J. Chem. Sci. 2015, 127, 1547–1556. doi:10.1007/
s12039-015-0923-x