Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives via SNAr amination reaction

Article abstract of DOI:10.1016/j.cclet.2014.10.007

An efficient and high-yielding synthesis of N²-arylaminopyrimidine-5-carbonitrile derivatives starting from arylamines and 2-methylthio-pyrimidine-5-carbonitrile derivatives has been developed in the presence of cesium carbonate as basic reagent. This new protocol showed high chemical tolerance for a range of functional groups, and only the methylthio substituent on C2 of the pyrimidine ring was replaced with arylamine derivatives under the reaction conditions.

Full text of DOI:10.1016/j.cclet.2014.10.007

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CCLET-3113; No. of Pages 5
Chinese Chemical Letters xxx (2014) xxx–xxx
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Chinese Chemical Letters
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Original article
Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives via
SNAr amination reaction
a
b
Shahnaz Rostamizadeh a, , Masoomeh Nojavan , Reza Aryan
*
a Department of Chemistry, Faculty of Science, K. N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran
b Department of Chemistry, Faculty of Science, University of Zabol, Zabol, Iran
A R T I C L E I N F O
A B S T R A C T
An efficient and high-yielding synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives starting
from arylamines and 2-methylthio-pyrimidine-5-carbonitrile derivatives has been developed in the
presence of cesium carbonate as basic reagent. This new protocol showed high chemical tolerance for a
range of functional groups, and only the methylthio substituent on C2 of the pyrimidine ring was
replaced with arylamine derivatives under the reaction conditions.
Article history:
Received 24 April 2014
Received in revised form 20 July 2014
Accepted 31 July 2014
Available online xxx
ß 2014 Shahnaz Rostamizadeh. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All
rights reserved.
Keywords:
N2-Arylaminopyrimidine-5-carbonitrile
derivatives
Pyrimidine-5-carbonitrile derivatives
C–N bond formation
SNAr mechanism
1. Introduction
[8,20–23]. In addition, Pd- or Cu-catalyzed coupling reactions
between heteroaryl thioethers and amines have also been reported
The N2-arylaminopyrimidines exhibit interesting pharma-
ceutical and agrochemical properties. This structural motif can
be found in a variety of biologically active compounds, such as
anticancer trademark agents, Pazopanib (VotrienTM) and Imitanib
(GleevecTM) [1–4], Fungicides [5] and anti-HIV agents, such as
IntelenceTM [6,7] (Fig. 1).
Because of the occurrence of aryl C–N bond in pharmaceuticals
and natural products, its synthesis has gained a broad attention in
the field of synthetic organic chemistry, leading to expanding
application in many total syntheses and the industrial preparation
of numerous pharmaceuticals [8–12]. A few approaches have
been reported for the synthesis of carbon–nitrogen bonds on the
aromatic rings via the reaction of amines with leaving groups such
as the alkylthio group. These procedures are classified into two
different sets of reactions: The oxidation of alkylthio to sulfone
prior to using amines as nucleophiles [13,14] and the direct
nucleophilic replacement of alkyl- and arylthio groups [15–19].
Recently, application of transition metal-catalyzed amination of
aryl halides in processes such as Goldberg and Buchwald-Hartwig
cross-coupling reactions were also developed for this purpose
as milder alternatives [24]. However, the use of toxic and
expensive transition metals is a significant limiting factor for
these processes and under Goldberg and Buchwald-Hartwig
amination conditions. 4-Amino-6-(4-chlorophenyl)-2-methylthio-
pyrimidine-5-carbonitrile 1b reacts at both the methylthio group
at the C2 of starting pyrimidine ring and 4-chlorophenyl ring on
the C6 leading to substitution products 2–4 (Scheme 1).
With a view of the above-mentioned considerations and in
continuation of our previous work for the synthesis of 4-amino-6-
aryl-2-methylthio-pyrimidine-5-carbonitrile derivatives [25], we
were encouraged to introduce a novel transition metal-free
protocol for the synthesis of new derivatives of 2-arylaminopyr-
imidine through the amination of 4-amino-6-aryl-2-methylthio-
pyrimidine-5-carbonitrile derivatives (Scheme 1).
To address this purpose, new synthetic strategies are needed
to be developed that would enable the facile synthesis of N2-
arylaminopyrimidines. Herein, we wish to describe a successful
strategy by which the desired product 2 can be achieved solely
with high yields under the SNAr reaction conditions, and the
possibility for the formation of side products would be excluded.
2. Experimental
*
Corresponding author.
Melting points were recorded on a Buchi B-540 apparatus. IR
spectra were recorded on an ABB Bomem Model FTLA200-100
E-mail addresses: shrostamizadeh@yahoo.com, rostamizadeh@hotmail.com
(S. Rostamizadeh).
http://dx.doi.org/10.1016/j.cclet.2014.10.007
1001-8417/ß 2014 Shahnaz Rostamizadeh. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Please cite this article in press as: S. Rostamizadeh, et al., Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives via SNAr
amination reaction, Chin. Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.10.007

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2.1. General procedure for the synthesis of 4-amino-6-aryl-2-
mthylthio pyrimidine-5-carbonitrile 1
Malononitrile (1 mmol), aldehyde (1 mmol), S-methyli-
sothiouronium iodide (1 mmol), and nanocatalyst MCM-41-NH2
(0.06 g) were ground and placed in a test tube. The reaction was
then stirred under heating for 1 h at 80 8C and monitored by TLC
(EtOAc:petroleum ether = 1:2). After completion of the reaction,
the reaction mixture was cooled to room temperature and added
EtOAc, and then the mixture was stirred for at least 10 min. The
reaction mixture was filtered off to remove the catalyst and
evaporated in vacuo to obtain a solid product. The residues were
further purified by crystallization from EtOH [25].
2.2. General procedure for the synthesis of 2a–2h
A mixture of 4-amino-6-aryl-2-mthylthiopyrimidine-5-carbo-
nitrile
1 (1 mmol), arylamine (1.2 mmol), cesium carbonate
Fig. 1. Biologically active compounds with N2-arylaminopyrimidine building block.
(1 mmol, 0.32 g) in 5 mL DMF was heated at 120 8C and monitored
Scheme 1. Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives under SNAr reaction condition and Goldberg and Buchwald-Hartwig amination condition.
instrument. 1H NMR and 13C NMR spectra were measured on a
Bruker DRX-300 spectrometer at 300 MHz and 75 MHz using TMS
as an internal standard. Chemical shifts (d) were reported relative
to TMS, and coupling constants (J) were reported in hertz (Hz).
Mass spectra were recorded on a Shimadzu QP 1100 EX mass
spectrometer with 70 eV ionization potential. Elemental analyses
of new compounds were performed with a Vario EL III 0 Serial No.
11024054 instrument and their results favorably agreed with the
calculated values.
by TLC (AcOEt:petroleum ether = 1:2). After completion of the
reaction, the reaction mixture was cooled to ambient temperature,
neutralized with 10% (v/v) HCl solution (20 mL) and was extracted
by ethyl acetate (20 mL Â 3). The combined organic layers were
dried over Na2SO4 and concentrated in vacuo. The solid residues
Table 1
Screening the effect of different solvents and various bases in the reaction of 4-
amino-6-(4-chlorophenyl)-2-methylthiopyrimidine-5-carbonitrile and aniline for
the formation of product 2c.
Entry Solvent
Metal catalyst Base
–
T (8C) Time (h) Product Yields (%)
1
2
2-Propanol –
Reflux 24
Reflux 24
–
–
–
t-BuOH
DMF
–
–
–
–
–
–
–
–
3
–
100
100
24
24
24
–
2
–
4
DMF
KOH
37
–
5
DMF
t-BuOK 100
–
6
t-BuOH
DMF
t-BuOK Reflux 24
–
–
7
Cs2CO3 100
8
8
2
63
33c
42c
39c
51c
32
–
8
DMF
CuIa (10%)
KOH
100
100
2,3,4
2,3,4
2,3,4
2,3,4
2
b
9
DMF
PdCl2 (10%) KOH
12
10
10
b
10
11
12
13
14
DMF
PdCl2 (10%) Cs2CO3 100
CuIa (10%)
Cs2CO3 100
DMF
1,4-Dioxan –
Cs2CO3 Reflux 24
Toluene
DMF
–
–
Cs2CO3 120
Cs2CO3 120
24
2
–
2
82
a
L
-Proline (20%) was used as ligand.
Triphenylphosfine (20%) was used as ligand.
Isolated yield of products mixture.
b
c
Scheme 2. Model reaction used for the synthesis of N2-arylaminopyrimidine-5-
carbonitrile derivatives.
Please cite this article in press as: S. Rostamizadeh, et al., Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives via SNAr
amination reaction, Chin. Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.10.007

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3
(KBr, cmÀ1):
(300 MHz, DMSO-d6):
7.06–7.09 (d, 2H, J = 8.6 Hz), 6.64–6.67 (d, 2H, J = 8.6 Hz); 13C NMR
(75 MHz, DMSO-d6): 174.4, 168.9, 168.0, 166.3, 135.9, 131.2,
n
3471, 3332, 3229, 2217, 1647, 1534; 1H NMR
d
7.82–7.85 (m, 2 H), 7.62–7.72 (m, 3H),
d
130.2, 128.8, 128.6, 116.1, 115.8, 111.1, 81.1; MS m/z: 321(87, M+),
320(100), 118(37), 77(22), 51(9); Anal. Calcd. for C17H12ClN5: C,
63.46; H, 3.76; Cl, 11.02; N, 21.77. Found: C, 63.61; H, 3.79; N,
21.58.
Scheme 3. Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives under
optimized reaction conditions.
4-Amino-6-(4-chlorophenyl)-2-((3, 4-dimethylphenyl)amino)-
pyrimidine-5-carbonitrile (2e): Pale yellow powder; mp: 256 8C;
were further purified by crystallization from EtOH to furnish the
desired N2-arylaminopyrimidine-5-carbonitrile product.
IR (KBr, cmÀ1):
(300 MHz, DMSO-d6):
n
3442, 3338, 3214, 2218, 1642, 1558; 1H NMR
d
9.66 (s, 1H, NH), 7.82–7.85 (d, 2H,
4-Amino-6-(4-chlorophenyl)-2-(phenylamino)pyrimidine-5-
carbonitrile (2b): Pale yellow powder; mp: 268–270 8C; IR
J = 8.3 Hz), 7.59–7.62 (d, 3H, J = 8.3 Hz), 7.48–7.51 (d, 1H,
J = 7.3 Hz), 6.99–7.02 (d, 1H, J = 8.2 Hz), 2.18 (s, 3H, CH3), 2.15
Table 2
Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives using cesium carbonate in DMF as solvent at 120 8C.
Entry
1
X
Y
Product
Structure
Time (h)
4
Yielda (%)
80
Mp (8C)
248
H
H
2a
NH2
NC
N
N
N
H
2
4-Cl
H
2b
4
82
268–270
NH2
NC
N
N
H
N
Cl
NH2
3
4
4-Cl
4-Cl
4-Cl
4-Br
2c
2
6
75
68
278–280
NC
NC
Cl
N
N
N
H
Cl
Cl
2d
NH2
261
Br
N
N
N
H
5
6
4-Cl
3,4-diCH3
2e
2f
2
4
91
85
256
235
NH2
NC
NC
NC
N
N
N
H
Cl
4-CN
H
NH2
N
N
N
H
NC
NC
O2N
7
8
4-CN
3,4-diCH3
2g
2h
2
2
95
78
207–208
239–241
NH2
N
N
N
H
4-NO2
H
NH2
NC
N
N
H
N
9
10
11
12
13
14
15
4-OCH3
4-CH3
2,4-diCl
H
4-Cl
–
–
–
–
–
–
–
8
8
8
8
8
8
8
–
–
–
–
–
–
–
–
–
–
–
–
–
–
4-Cl
4-Cl
4-NO2
4-NO2
4-NO2
4-NO2
4-Cl
4-CN
4-NO2
a
Isolated yield.
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amination reaction, Chin. Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.10.007

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Scheme 4. The SNAr mechanism for the formation of N2-arylaminopyrimidine-5-carbonitrile derivatives 2.
(s, 3H, CH3); 13C NMR (75 MHz, DMSO-d6):
d
167.4, 164.6, 160.1,
(Scheme 4) [26,27]. The use of heavier alkali metal carbonates such
as cesium carbonate seemed to provide advantages over the other
members of this class of compounds in terms of yield and the
reaction rate as previously reported [28].
140.9, 137.3, 135.9, 130.6, 130.1, 129.4, 120.8, 119.0, 117.6, 116.0,
112.5, 66.3, 19.6, 18.7; MS m/z: 247(29), 198(38), 139(100),
111(52), 75(49), 50(22); Anal. Calcd. for C19H16ClN5: C, 65.24; H,
4.61; Cl, 10.13; N, 20.02. Found: C, 65.53; H, 4.72; N, 19.79.
4. Conclusion
3. Results and discussion
In conclusion, we have demonstrated the new procedure for the
preparation of N2-arylaminopyrimidine-5-carbonitrile derivatives
through the substitution of the methylthio group with arylamines.
Unlike the metal catalyzed substitution reaction, no substitution of
halide atom took place at the aryl group on C6 position as a side
reaction. The reaction provides the easy access to the synthesis of
interesting N2-aryl pyrimidine-5-carbonitrile heterocycles in good
to excellent yields of the products. Relatively short reaction times
and milder reaction temperature are the other advantages of the
present method in comparison to the previous reports. Finally, it
should be pointed out that the reaction seems to follow a pathway
in which a Meisenheimer complex is involved.
Initially, in order to obtain the desired product 2, the reaction
of 4-amino-6-(4-chlorophenyl)-2-methylthio-pyrimidine-5-car-
bonitrile 1b (1 mmol), with 1.2 mmol of 4-chloroaniline was
investigated in different solvents and in the presence of various
bases, ligands and catalysts (Scheme 2, Table 1).
The best results were obtained using cesium carbonate in DMF
as solvent at 120 8C without using any ligands (Table 1, entry 14).
The reaction in Scheme 2 was also studied under different amount
of cesium carbonate, and the best results were obtained using
0.32 g (1 mmol, equimolar to the reactants) of cesium carbonate.
Increasing the amount of base did not affect the reaction time
and yield but decreased amounts of cesium carbonate lead to
prolonged reaction times (up to 12 h) and lower yields of the
products. The reaction conditions used in the present work are very
similar (in terms of reaction times, amount of base, and
temperature) to transition metal catalyzed processes.
References
[1] R. Capdeville, E. Buchdunger, J. Zimmermann, et al., Glivec (STI571, imatinib), a
rationally developed, targeted anticancer drug, Nat. Rev. Drug Discov. 1 (2002)
493–502.
[2] Z. Lin, F. Junhua, C. Jer-Hong, et al., Design, synthesis, and biological evaluation of
pyrazolopyrimidine–sulfonamides as potent multiple-mitotic kinase (MMK) inhi-
bitors (Part I), Bioorg. Med. Chem. Lett. 21 (2011) 5633–5637.
[3] L.A. McDermott, M. Simcox, B. Higgins, et al., RO4383596, an orally active KDR,
FGFR, and PDGFR inhibitor: synthesis and biological evaluation, Bioorg. Med.
Chem. 13 (2005) 4835–4841.
To explore the scope and generality of this reaction, we
repeated this process for various substituted 2-methylthiopyr-
imidine-5-carbonitrils and arylamine derivatives, in the presence
of cesium carbonate in DMF as solvent (Scheme 3). The reaction
proceeded efficiently with various substituted 2-methylthio-
pyrimidine-5-carbonitrile derivatives (Table 2).
[4] M. Sabat, J.C. VanRens, T.A. Brugel, et al., The development of novel 1,2-dihydro-
pyrimido[4,5-c]pyridazine based inhibitors of lymphocyte specific kinase (Lck),
Bioorg. Med. Chem. Lett. 16 (2006) 4257–4261.
As indicated in Table 2, when the pyrimidine derivatives with
electron releasing groups or bulky substituent on aryl ring at C6
position were used, the reaction did not proceed at all (entries 9–
11, Table 2). The case of no product formation when Me and OMe
substituents are placed on 6-aryl ring can be explained by
comparing the Hammett substituent constants for methyl,
methoxy (entries 9 and 10, Table 2) with chlorine (entry 3,
[5] U.J. Heye, J. Speich, H. Siegle, et al., CGA 219417:
fungicide, Crop Prot. 13 (1994) 541–549.
a novel broad-spectrum
[6] L.B. Johnson, L.D. Saravolatz, Etravirine, a next-generation nonnucleoside reverse-
transcriptase inhibitor, Clin. Infect. Dis. 48 (2009) 1123–1128.
[7] X.Q. Feng, Y.H. Liang, Z.S. Zeng, et al., Structural modifications of DAPY analogues
with potent anti-HIV-1 activity, Chem. Med. Chem. 4 (2009) 219–224.
[8] J.F. Hartwig, Approaches to catalyst discovery. New carbon-heteroatom and
carbon–carbon bond formation, Pure Appl. Chem. 71 (1999) 1417–1423.
[9] A.R. Muci, S.L. Buchwald, Practical palladium catalysts for C–N and C–O bond
formation, Top. Curr. Chem. 219 (2002) 131–209.
[10] J.F. Hartwig, Carbon-heteroatom bond-forming reductive eliminations of amines,
ethers, and sulfides, Acc. Chem. Res. 31 (1998) 852–860.
[11] J.F. Hartwig, Transition metal catalyzed synthesis of arylamines and aryl ethers
from aryl halides and triflates: scope and mechanism, Angew. Chem. Int. Ed. 37
(1998) 2046–2067.
[12] D.S. Surry, S.L. Buchwald, Biaryl phosphane ligands in palladium-catalyzed ami-
nation, Angew. Chem. Int. Ed. 47 (2008) 6338–6361.
[13] S.N. VanderWel, P.J. Harvey, D.J. McNamara, et al., Pyrido[2,3-d]pyrimidin-7-ones
as specific inhibitors of cyclin-dependent kinase 4, J. Med. Chem. 48 (2005) 2371–
2387.
[14] K.L. Sayle, J. Bentley, F.T. Boyle, et al., Structure-based design of 2-arylamino-4-
cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent
kinases 1 and 2, Bioorg. Med. Chem. Lett. 13 (2003) 3079–3082.
[15] M.L. Maddess, R. Carter, SNAr reactions of 2-methylthio-4-pyrimidinones in
pivalic acid: access to functionalized pyrimidinones and pyrimidines, Synthesis
44 (2012) 1109–1118.
Table 2). The
0.23 respectively. This implies that because of electron-donating
character of methyl and methoxy (negative values for P) the six
s
P for methyl, methoxy and Cl are À0.17, À0.27 and
s
aryl and pyrimidine rings are consequently more electron-rich to
be attacked by aniline derivatives. Instead, the chlorine atom
withdraws electrons from the aryl ring leading to consecutive
electron deficiency in pyrimidine ring and facilitates the nucleo-
philic attack by aniline derivative. Also, 4-nitroaniline did not react
with reactive electron-poor pyrimidine derivatives because of the
sP constant for NO2 which equals to 0.78 (intensively electron-
withdrawing) (entries 12–15, Table 2).
A SNAr (addition–elimination) mechanism under basic condi-
tion is shown for the formation of N2-arylaminopyrimidine-5-
carbonitrile derivatives 2 in Scheme 4. First, anionic arylamine
generated by cesium carbonate as base, attacks the C2 of
pyrimidine ring as a nucleophile. Then, the resulting stable
Meisenheimer complex releases thiolate anion as leaving group
and transforms to the desired product 2 through aromatization
[16] J. Spychala, A facile preparation N2-arylisocytosines, Synth. Commun. 27 (1997)
1943–1949.
[17] M. Barvian, D.H. Boschelli, J. Cossrow, et al., Pyrido[2,3-d]pyrimidin-7-one inhi-
bitors of cyclin-dependent kinases, J. Med. Chem. 43 (2000) 4606–4616.
[18] J. Spychala, K. Golankiewicz, The efficient method of synthesis of 4-N-arylcyto-
sines, Synth. Commun. 20 (1990) 1899–1904.
Please cite this article in press as: S. Rostamizadeh, et al., Synthesis of N2-arylaminopyrimidine-5-carbonitrile derivatives via SNAr
amination reaction, Chin. Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.10.007

G Model
CCLET-3113; No. of Pages 5
S. Rostamizadeh et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
5
[19] B. Sreedhar, P.S. Reddy, M.A. Reddy, Catalyst-free and base-free water-
promoted SNAr reaction of heteroaryl halides with thiols, Synthesis 10 (2009)
1732–1738.
[24] L. Pellegatti, E. Vedrenne, J.M. Leger, et al., First efficient palladium-catalyzed
aminations of pyrimidines, 1,2,4-triazines and tetrazines by original methyl
sulfur release, Synlett 13 (2009) 2137–2142.
[20] R.A. Altman, S.L. Buchwald, Cu-catalyzed Goldberg and Ullmann reactions of
aryl halides using chelating N- and O-based ligands, Nat. Protoc. 2 (2007) 2474–
2479.
[21] Y. Liu, Y. Bai, J. Zhang, et al., Optimization of the conditions for copper-
mediated N-arylation of heteroarylamines, Eur. J. Org. Chem. (2007) 6084–
6088.
[25] Sh. Rostamizadeh, M. Nojavan, An environmentally benign multicomponent
synthesis of some novel 2-methylthio pyrimidine derivatives using MCM-41-
NH2 as nanoreactor and nanocatalyst, J. Heterocycl. Chem. 51 (2014) 418–422.
[26] C.F. Bernasconi, M.C. Muller, P. Schmid, Intermediates in nucleophilic aromatic
substitution. 20. Rate-limiting proton transfer in the formation of Meisenheimer
complexes between 1,3,5-trinitrobenzene and amines. The effect of dimethyl
sulfoxide on proton-transfer rates. Relative leaving-group abilities of amines and
alkoxide ions, J. Org. Chem. 44 (1979) 3189–3196.
[22] J.H.M. Lange, L.J.F. Hofmeyer, F.A.S. Hout, et al., Microwave-enhanced Goldberg
reaction:
a novel route to N-arylpiperazinones and N-arylpiperazinediones,
Tetrahedron Lett. 43 (2002) 1101–1104.
[27] I. Gallardo, G. Guirado, J. Marquet, Nucleophilic aromatic substitution for heteroa-
toms: an oxidative electrochemical approach, J. Org. Chem. 67 (2002) 2548–2555.
[28] T. Flessner, S. Doye, Cesium carbonate: a powerful inorganic base in organic
synthesis, J. Prakt. Chem. 341 (1999) 186–190.
[23] J. Ahmadi, S. Sadjadi, M. Hosseinpour, Granulated copper oxide nano-catalyst: a
novel and efficient catalyst for C–N cross-coupling of amines with iodobenzene,
Monatsh. Chem. 142 (2011) 801–806.
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amination reaction, Chin. Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.10.007