Crown ether complex cation ionic liquids: synthesis and catalytic applications for the synthesis of tetrahydro-4H-chromene and 1,4-dihydropyridine derivatives

Article abstract of DOI:10.1080/17415993.2017.1293058

A series of crown ether complex cation ionic liquids (CECILs) are synthesized by crown ethers chelated with sodium benzenesulfonates, and used as a green and environmental catalyst, for the synthesis of tetrahydro-4H-chromene and 1,4-dihydropyridine deriv

Full text of DOI:10.1080/17415993.2017.1293058

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Crown ether complex cation ionic liquids:
synthesis and catalytic applications for the
synthesis of tetrahydro-4H-chromene and 1,4-
dihydropyridine derivatives
Mehdi Abaszadeh & Mohammad Seifi
To cite this article: Mehdi Abaszadeh & Mohammad Seifi (2017): Crown ether complex cation
ionic liquids: synthesis and catalytic applications for the synthesis of tetrahydro-4H-chromene and
1,4-dihydropyridine derivatives, Journal of Sulfur Chemistry
To link to this article: http://dx.doi.org/10.1080/17415993.2017.1293058
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Date: 01 March 2017, At: 00:08

JOURNAL OF SULFUR CHEMISTRY, 2017
http://dx.doi.org/10.1080/17415993.2017.1293058
Crown ether complex cation ionic liquids: synthesis and
catalytic applications for the synthesis of
tetrahydro-4H-chromene and 1,4-dihydropyridine derivatives
Mehdi Abaszadeha and Mohammad Seifib
aPharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences,
Kerman, Iran; bDepartment of Chemistry, Faculty of Sciences, Najafabad Branch, Islamic Azad University,
Najafabad, Esfahan, Iran
ABSTRACT
ARTICLE HISTORY
Received 26 November 2016
Accepted 1 February 2017
A series of crown ether complex cation ionic liquids (CECILs) are syn-
thesized by crown ethers chelated with sodium benzenesulfonates,
and used as a green and environmental catalyst, for the synthesis
of tetrahydro-4H-chromene and 1,4-dihydropyridine derivatives by
three-component reactions of aromatic aldehydes and malononitrile
with cyclic β-dicarbonyls or cyclic β-enaminoketones respectively, in
H2O/EtOH (1:1), at the reflux condition. CECILs, as a green and envi-
ronmental catalyst, can be easily obtained and are stable. Further-
more, high conversions, short reaction times, and cleaner reaction
profiles are some of the advantages of this method.
KEYWORDS
Crown ether complex cation
ionic liquids; crown ethers;
sodium benzenesulfonates;
tetrahydro-4H-chromene;
1,4-dihydropyridine
1. Introduction
Ionic liquids (ILs) have attracted significant attention from research groups because of their
unique properties and novel applications. ILs exhibit several properties such as low vapor
pressure, recyclability, excellent thermal stability and desirable solvating properties [1]. ILs
have attracted remarkable attention as new materials for various chemical applications.
There are reports on ILs which consist of strong Lewis-acidic metal cations such as lithium
ion and potassium ion coordinated by ether-ligands to decrease charge density [2,3]. ILs
CONTACT Mehdi Abaszadeh
abaszadeh@kmu.ac.ir
Pharmaceutics Research Center, Institute of
Neuropharmacology, Kerman University of Medical Sciences, Kerman 76175493, Iran
© 2017 Informa UK Limited, trading as Taylor & Francis Group

2
M. ABASZADEH AND M. SEIFI
have been used in many organic reactions – for example, SN2 process [4–8], hydrogenation,
oxidation [9–12], three-component reactions [13,14], and carbon–carbon bond-forming
reactions, such as Michael addition [15], Henry reaction [16], Knoevenagel condensation
and Heck reaction [3,17].
Tetrahydro-4H-chromenes, due to their lucrative biological and pharmacological prop-
erties, are used as an important class of heterocyclic compounds in the pharmaceutical
applications, such as anticancer [18], antimalarial [19], antileishmanial [20], antibac-
terial [21], antifungal [22], antianaphylactic [23], antiallergenic [24], diuretic [25] and
hypotensive [26] agents.
Also, 1,4-dihydropyridines are an important class of compounds with a wide range of
biological activities [27]. Due to being pharmacologically active and acting as antitumor
[28], calcium channel blocker [29], antitubercular [30], analgesic [31], antithrombotic [32],
anti-inflammatory [33], anticonvulsant agents [34], and they are of many interests.
Applications of tetrahydro-4H-chromene and 1,4-dihydropyridine derivatives neces-
sitate the advancement in environmental-friendly procedures to synthesize these com-
pounds by three-component reactions of aromatic aldehydes and malononitrile with cyclic
β-dicarbonyls or cyclic β-enaminoketones, respectively. There are various catalytic systems
for the synthesis of tetrahydro-4H-chromene [35–44] and 1,4-dihydropyridine [45–47]
derivatives by MCR, but these systems suffer from disadvantages such as the use of
toxic organic solvents, costly catalysts, existence of transition metals, difficult work up,
time-consuming reactions and low yield. Thus, a simple and green synthesis of tetrahydro-
4H-chromenes and 1,4-dihydropyridines needs to be carried out without association of
these catalytic systems.
Only a few reports are available on the synthesis of crown ether complex cation ionic
liquids (CECILs), by crown ethers chelated with alkali metal cations [48–51]. Herein, we
synthesize a series of CECILs (CECILs) (3a–f) by crown ethers (1a, 1b) chelated with
sodium benzenesulfonates (2a–c), and used as a green and environmental catalyst, for the
synthesis of tetrahydro-4H-chromene (7a–v) and 1,4-dihydropyridine (10a–p) derivatives
by the three-component reaction of aromatic aldehydes (4a–j) and malononitrile (5) with
cyclic β-dicarbonyls (6a, b) or cyclic β-enaminoketone (9a–d) respectively, in H2O/EtOH
(1:1), at reflux condition.
2. Results and discussion
Initially, the 18-crown-6 (1a) and sodium benzenesulfonate (2a) were mixed and dis-
solved in water; the desired 18-crown-6 complex cation ionic liquid (CECIL) (3a) was not
obtained as a clear solution due to the poor solubility of 18-crown-6. Strangely, when the
solvent was changed to methanol, a clear solution was obtained after stirring for 1 h at
60°C, and vacuum drying the desired CECIL (3a) to generate it in 100% yield. Then, we
dissolved the crown ethers (1a, 1b) and sodium benzenesulfonates (2a–c) in methanol to
generate our desirable CECILs (3a–f) (Scheme 1). CECILs are very soluble in water, readily
soluble in polar solvents, such as methanol, ethanol and acetone, and insoluble in nonpolar
solvents, such as alkanes, ethers and aromatic hydrocarbons.
Afterwards, in continuation of our previous works on environmental-friendly multi-
component reactions [52–54], we used CECILs, as a green and environmental catalyst, for

JOURNAL OF SULFUR CHEMISTRY
3
Scheme 1. Synthesis of CECILs (3a–f).
Scheme 2. Synthesis of tetrahydro-4H-chromene (7a–v) and 1,4-dihydropyridine (10a–p) derivatives.
the synthesis of tetrahydro-4H-chromene (7a–v) and 1,4-dihydropyridine (10a–p) deriva-
tives by the three-component reaction of aromatic aldehydes (4a–j) and malononitrile
(5) with cyclic β-dicarbonyls (6a, b) or cyclic β-enaminoketone (9a–d) respectively, in
H2O/EtOH (1:1), at reflux condition (Scheme 2).
To optimize the reaction conditions, a methodical study considering different variables
affecting the reaction time and yield was carried out the three-component reaction of ben-
zaldehyde 4a, malononitrile 5 and 5,5-dimethylcyclohexane-1,3-dione 6a in the presence
of CECILs as catalysts for preparing compound 2-amino-7,7-dimethyl-5-oxo-4-phenyl-
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile 7a (Scheme 2). The results are shown in
Table 1.

4
M. ABASZADEH AND M. SEIFI
Table 1. Optimization of the model reaction between benzaldehyde 4a, malononitrile 5 and 5,5-
dimethylcyclohexane-1,3-dione 6a.
Entry
Solvent
Catalyst
Catalyst (mol %)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
H2O/EtOH
H2O/EtOH
H2O/EtOH
H2O/EtOH
H2O/EtOH
H2O/EtOH
H2O/EtOH
H2O/EtOH
[18-C-6Na][C6H5-SO3]
30
30
30
30
30
30
20
40
25
20
30
35
25
40
10
20
90
92
87
88
89
85
90
92
[18-C-6Na][3-NO2-C6H4-SO3]
[18-C-6Na][4-CH3-C6H4-SO3]
[Dibenzo 18-C-6Na][C6H5-SO3]
[Dibenzo 18-C-6Na][3-NO2-C6H4-SO3]
[Dibenzo 18-C-6Na][4-CH3-C6H4-SO3]
[18-C-6Na][3-NO2-C6H4-SO3]
[18-C-6Na][3-NO2-C6H4-SO3]
We used CECILs (3a–f) in this reaction and the best results in terms of reaction time
and yield of the desired product 7a were obtained when the reaction was conducted in
[18-C-6Na][3-NO2-C6H4-SO3] (Table 1, entries 1–6). We also optimized the quantity of
catalysts. The best results were obtained when the reactions were carried out in the presence
of 30 mol% [18-C-6Na][3-NO2-C6H4-SO3] (Table 1, entries 7, 8).
According to our collected data, we decided to apply this method for the synthesis
of tetrahydro-4H-chromene (7a–v) and 1,4-dihydropyridine (10a–p) derivatives by the
three-component reaction of aromatic aldehydes (4a–j) and malononitrile (5) with cyclic
β-dicarbonyls (6a, b) or cyclic β-enaminoketone (9a–d), respectively, in H2O/EtOH (1:1),
at reflux condition (Scheme 2 and Tables 2 and 3).
Table 2. Three-component reaction of aromatic aldehydes (4a–j), malononitrile (5) and dimedone (6a)
or 1,3-cyclohexanedione (6b).
Compd. No.
R
Ar
Time(min)
Yield (%)
M. P. observed (°C)
M. P. reported (°C)
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
7q
7r
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
H
H
H
H
H
H
H
H
C6H5
4-Cl-C6H4
2,4-(Cl)2-C6H3
4-Br-C6H4
4-NO2-C6H4
4-CH3-C6H4
4-CH3O-C6H4
4-OH-C6H4
Furan-2-yl
Thiophen-2-yl
Pyridin-3-yl
C6H5
4-Cl-C6H4
2,4-(Cl)2-C6H3
4-Br-C6H4
4-NO2-C6H4
4-CH3-C6H4
4-CH3O-C6H4
4-OH-C6H4
Furan-2-yl
8
7
7
8
7
10
10
12
12
13
13
9
8
7
8
7
12
12
15
17
17
17
91
92
92
92
93
89
88
85
88
87
86
90
91
92
91
92
89
87
85
86
86
85
231–232
215–217
175–178
221–222
181–182
218–220
200–202
225–228
221–222
227–229
206–207
230–231
223–226
220–222
248–250
234–237
223–225
189–191
256–258
237–239
210–211
229–230
234–236 [35]
216–218 [35]
178–179 [37]
222–224 [35]
180–182 [35]
219–221 [35]
201–203 [35]
226–228 [35]
220–222 [35]
226–228 [35]
206–207 [43]
229–231 [37]
225–227 [37]
221–223 [37]
248–250 [43]
235–237 [37]
224–226 [36]
190–192 [37]
257–259 [36]
237–239 [43]
210–211 [43]
229–230 [43]
7s
7t
7u
7v
H
H
Thiophen-2-yl
Pyridin-3-yl

JOURNAL OF SULFUR CHEMISTRY
5
Table 3. Three-component reaction of aromatic aldehydes (4a–f), malononitrile (5) and cyclic enam-
inoketones (9a–d).
Compd. No.
R
R’
Ar
Time (min)
Yield (%)
M. P. observed (°C)
M. P. reported (°C)
10a
10b
10c
10d
10e
10f
10g
10h
10i
10j
10k
10l
10m
10n
10o
10p
Me
Me
Me
Me
Me
Me
Me
Me
H
H
H
H
H
H
H
H
C6H5
15
18
12
16
12
15
10
15
18
20
15
18
15
18
12
17
89
88
91
88
90
90
91
89
87
85
90
87
89
87
91
88
262–264
279–281
210 (dec.)
248–250
244–245
243–245
269–271
265–267
254 (dec.)
269–271
296–298
287–289
110 (dec.)
235 (dec.)
228–230
237–238
265–267 [45]
279–281 [46]
210 (dec.)[46]
248–250 [54]
246–248 [45]
243–245 [46]
269–271 [46]
265–267 [54]
254 (dec.) [46]
269–271 [46]
296–298 [46]
287–289 [54]
110 (dec.) [46]
235 (dec.) [46]
228–230 [46]
237–238 [54]
4-CH3O-C6H4
4-Br-C6H4
Pyridin-3-yl
C6H5
4-CH3-C6H4
4-Br-C6H4
Pyridin-3-yl
C6H5
4-CH3-C6H4
4-Cl-C6H4
Pyridin-3-yl
C6H5
4-CH3-C6H4
4-Cl-C6H4
Pyridin-3-yl
H
C6H5
C6H5
C6H5
C6H5
H
H
H
H
C6H5
C6H5
C6H5
C6H5
H
H
H
3. Experimental section
3.1. General methods
Melting points were measured on an Electrothermal-9100 apparatus and are uncorrected.
IR spectra were recorded on a Brucker FT-IR Tensor 27 infrared spectrophotometer. 1H
NMR spectra were recorded on a Brucker Avance III 400, 300 MHz spectrometer. 13C
NMR spectra were recorded on the same instruments at 75 MHz using tetramethylsilane as
an internal standard. Elemental analyses were performed using a Heracus CHN-S/O-Rapid
analyser.
3.2. General procedure for the synthesis of CECILs (3a–f)
The sodium benzenesulfonates (2a–c) (2 mmol) with crown ethers (1a, 1b) (2 mmol) in
15 mL methanol were stirred for 1 h at 60°C. Then methanol was removed under reduced
pressure. The residue was vacuum dried to generate the desired CECIL in 100% yield.
1
[18-C-6Na][C6H5-SO3] (3a). Liquid; H NMR (300 MHz, D2O) δppm: 7.73 (d, 2H,
J = 4 Hz, Ar), 7.49–7.43 (m, 3H, Ar), 3.53 (s, 24H, OCH2); 13C NMR (75 MHz, D2O) δ
:
ppm
142.63, 131.48, 128.97, 125.37, 69.33 (OCH2). Anal. calcd. for C18H29NaO9S: C, 48.64; H,
6.58; S, 7.21%. Found: C, 48.47; H, 6.41; S, 7.05%.
[18-C-6Na][3-NO2-C6H4-SO3] (3b). Yellow powder; mp 107–109°C; 1H NMR
(300 MHz, D2O) δppm: 8.48 (s, 1H, Ar), 8.28 (d, 1H, J = 4 Hz, Ar), 8.07 (d, 1H,
J = 4 Hz, Ar), 7.67 (t, 1H, J = 4 Hz, Ar), 3.57 (s, 24H, OCH2); 13C NMR (75 MHz,
D2O) δppm: 147.70, 144.36, 131.82, 130.58, 125.99, 120.64, 69.38 (OCH2). Anal. calcd. for
C18H28NNaO11S: C, 44.17; H, 5.77; N, 2.86; S, 6.55%. Found: C, 43.99; H, 5.59; N, 2.69; S,
6.39%.

6
M. ABASZADEH AND M. SEIFI
[18-C-6Na][4-CH3-C6H4-SO3] (3c). White powder; mp 79–81°C; 1H NMR (300 MHz,
D2O) δppm: 7.59 (d, 2H, J = 4 Hz, Ar), 7.25 (d, 2H, J = 4 Hz, Ar), 3.53 (s, 24H, OCH2),
2.28 (s, 3H, CH3); 13C NMR (75 MHz, D2O) δppm: 142.26, 139.67, 129.42, 125.36, 69.35
(OCH2), 20.50 (CH3). Anal. calcd. for C19H31NaO9S: C, 49.77; H, 6.82; S, 6.99%. Found:
C, 49.58; H, 6.65; S, 6.82%.
[Dibenzo 18-C-6Na][C6H5-SO3] (3d). White powder; mp >300°C; 1H NMR
(300 MHz, DMSO-d6) δppm: 7.69–6.90 (m, 13H, Ar), 4.09 (t, 8H, J = 3 Hz, OCH2),
3.91 (t, 8H, J = 3 Hz, OCH2); 13C NMR (75 MHz, DMSO-d6) δppm: 148.82, 147.64,
128.91, 128.12, 126.01, 121.13, 111.65, 68.88 (OCH2), 67.24 (OCH2). Anal. calcd. for
C26H29NaO9S: C, 57.77; H, 5.41; S, 5.93%. Found: C, 57.59; H, 5.25; S, 5.76%.
[Dibenzo 18-C-6Na][3-NO2-C6H4-SO3] (3e). Yellow powder; mp >300°C; 1H NMR
(300 MHz, DMSO-d6) δppm: 8.42 (s, 1H, Ar), 8.22 (d, 1H, J = 4 Hz, Ar), 8.09 (d, 1H,
J = 4 Hz, Ar), 7.68 (t, 1H, J = 4 Hz, Ar), 6.99–6.89 (m, 8H, Ar), 4.10 (t, 8H, J = 3 Hz,
OCH2), 3.93 (t, 8H, J = 3 Hz, OCH2); 13C NMR (75 MHz, DMSO-d6) δppm: 150.41,
147.68, 147.60, 132.51, 130.30, 123.90, 121.11, 111.58, 68.87 (OCH2), 67.20 (OCH2). Anal.
calcd. for C26H28NNaO11S: C, 53.33; H, 4.82; N, 2.39; S, 5.48%. Found: C, 53.16; H, 4.65;
N, 2.21; S, 5.31%.
[Dibenzo 18-C-6Na][4-CH3-C6H4-SO3] (3f). White powder; mp >300°C; 1H NMR
(300 MHz, DMSO-d6) δppm: 7.56 (d, 2H, J = 4 Hz, Ar), 7.14 (d, 2H, J = 4 Hz, Ar),
7.00–6.90 (m, 8H, Ar), 4.09 (t, 8H, J = 3 Hz, OCH2), 3.92 (t, 8H, J = 3 Hz, OCH2), 2.31
(s, 3H, CH3); 13C NMR (75 MHz, DMSO-d6) δppm: 147.65, 146.20, 138.15, 128.54, 126.04,
121.12, 111.65, 68.88 (OCH2), 67.25 (OCH2), 21.28 (CH3). Anal. calcd. for C27H31NaO9S:
C, 58.48; H, 5.63; S, 5.78%. Found: C, 58.30; H, 5.46; S, 5.61%.
3.2.1. General procedure for the preparation of tetrahydro-4H-chromene (7a–v) and
1,4-dihydropyridine (10a–p) derivatives
A mixture of aromatic aldehydes 4a–j (2 mmol), malononitrile 5 (2 mmol), cyclic
β-dicarbonyls 6a, b or cyclic β-enaminoketones 9a–d (2 mmol) and [18-C-6Na][3-NO2-
C6H4-SO3] (30 mol%) in H2O/EtOH (1:1) (10 mL) was refluxed for in the reported time
in Tables 2 and 3 (the progress of the reaction was monitored by TLC and hexane/ethyl
acetate was used as an eluent). After completion of the reaction, the reaction mixture was
cooled, and the crude product was filtered and dried. The NMR spectra collected for 7i
and 7j [35]; 7k, 7t, 7u and 7v [43]; 10b, 10g, 10k and 10n [46] are consistent with the
previously reported NMR data for these compounds.
2-Amino-4-(furan-2-yl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-
carbonitrile (7i). Yellow powder; IR (KBr, νmax/cm−1): 3408, 3328 (NH2), 2192
1
−
−
(CN), 1680 (C O), 1600, 1555 (C C). H NMR (400 MHz, DMSO-d6) δppm: 7.46
(d, 3JHH = 4 Hz, CH-Ar), 7.07 (s, 2H, NH2), 6.30–6.04 (m, 2H, CH-Ar), 4.30 (s, 1H, CH),
2.47 (d, 2JHH = 8 Hz, CH), 2.40 (d, 2JHH = 8 Hz, CH), 2.27 (d, 2JHH = 8 Hz, CH), 2.15
(d, 2JHH = 8 Hz, CH), 1.03 (s, 3H, CH3), 0.97 (s, 3H, CH3).
2-Amino-7,7-dimethyl-5-oxo-4-(thiophen-2-yl)-5,6,7,8-tetrahydro-4H-chromene-
3-carbonitrile (7j). White powder; IR (KBr, νmax/cm−1): 3392, 3328 (NH2), 2192
1
−
−
(CN), 1673 (C O), 1596, 1539 (C C). H NMR (400 MHz, DMSO-d6) δppm: 7.30 (d,
3JHH = 4 Hz, CH-Ar), 7.10 (s, 2H, NH2), 6.88–6.84 (m, 2H, CH-Ar), 4.51 (s, 1H, CH),
2.45 (d, 2JHH = 8 Hz, CH), 2.40 (d, 2JHH = 8 Hz, CH), 2.28 (d, 2JHH = 8 Hz, CH), 2.13
(d, 2JHH = 8 Hz, CH), 1.02 (s, 3H, CH3), 0.95 (s, 3H, CH3).

JOURNAL OF SULFUR CHEMISTRY
7
2-Amino-7,7-dimethyl-5-oxo-4-(pyridin-3-yl)-5,6,7,8-tetrahydro-4H-chromene-3-
carbonitrile (7k). White powder; IR (KBr, νmax/cm−1): 3392, 3312 (NH2), 2192 (CN),
1
−
−
1680 (C O), 1596, 1574 (C C). H NMR (400 MHz, DMSO-d6) δppm: 8.37 (s, 2H,
NH2), 7.52–7.10 (m, 4H, CH-Ar), 4.22 (s, 1H, CH), 2.47 (d, 2JHH = 8 Hz, CH), 2.39 (d,
2JHH = 8 Hz, CH), 2.22 (d, JHH = 8 Hz, CH), 2.09 (d, JHH = 8 Hz, CH), 1.01 (s, 3H,
2
2
CH3), 0.92 (s, 3H, CH3).
2-Amino-4-(furan-2-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
(7t). Brown powder; IR (KBr, νmax/cm−1): 3408, 3328 (NH2), 2192 (CN), 1680 (C O),
1596, 1587 (C C). H NMR (400 MHz, DMSO-d6) δppm: 7.45 (d, JHH = 4 Hz, CH-
Ar), 7.05 (s, 2H, NH2), 6.28–6.02 (m, 2H, CH-Ar), 4.30 (s, 1H, CH), 2.47-1.93 (m, 6H,
3CH2).
−
1
3
−
2-Amino-5-oxo-4-(thiophen-2-yl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
(7u). White powder; IR (KBr, νmax/cm−1): 3424, 3344 (NH2), 2192 (CN), 1680 (C O),
−
1
1596, 1580 (C C). H NMR (400 MHz, DMSO-d6) δppm: 7.29 (d, 3JHH = 4 Hz, CH-Ar),
−
7.11 (s, 2H, NH2), 6.88-6.83 (m, 2H, CH-Ar), 4.51 (s, 1H, CH), 2.48–1.85 (m, 6H, 3CH2).
2-Amino-5-oxo-4-(pyridin-3-yl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
(7v). White powder; IR (KBr, νmax/cm−1): 3360, 3312 (NH2), 2192 (CN), 1664 (C O),
1580, 1542 (C C). H NMR (400 MHz, DMSO-d6) δppm: 8.38 (s, 2H, NH2), 7.53–7.09
(m, 2H, CH-Ar), 4.21 (s, 1H, CH), 2.47–1.92 (m, 6H, 3CH2).
−
1
−
2-Amino-4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoli
ne-3-carbonitrile (10b) Yellow crystals; IR (KBr, νmax/cm−1): 3392, 3328, 3232 (NH2,
1
−
−
NH), 2192 (CN), 1654 (C O), 1596 (C C). H NMR (400 MHz, DMSO-d6): 8.82 (s, 1H,
NH), 6.94 (d, 2H, JH−H = 4 Hz, CH-Ar), 6.71 (d, 2H, 3JH−H = 4 Hz, CH-Ar), 5.65 (s,
3
2
2H, NH2), 4.16 (s, 1H, CH), 3.61 (s, 3H, OCH3), 2.32 (d, JH−H = 8 Hz, CH), 2.20 (d,
2JH−H = 8 Hz, CH), 2.08 (d, 2JH−H = 8 Hz, CH), 1.89 (d, 2JH−H = 8 Hz, CH), 0.92, 0.81
(s, 6H, 2CH3).
2-Amino-4-(4-bromophenyl)-7,7-dimethyl-5-oxo-1-phenyl-1,4,5,6,7,8-hexahydro
quinoline-3-carbonitrile (10 g) White crystals; IR (KBr, νmax/cm−1): 3456, 3328 (NH2),
1
−
−
2160 (CN), 1648 (C O), 1587 (C C). H NMR (400 MHz, DMSO-d6): 7.63–7.23 (m,
2
9H, CH-Ar), 5.71 (s, 2H, NH2), 4.46 (s, 1H, CH), 2.21 (d, JH−H = 4 Hz, CH), 2.17 (d,
2JH−H = 4 Hz, CH), 2.01 (d, 2JH−H = 8 Hz, CH), 1.70 (d, 2JH−H = 8 Hz, CH), 0.88, 0.73
(s, 6H, 2CH3).
2-Amino-4-(4-chlorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile
(10k) Yellow crystals; IR (KBr, νmax/cm−1): 3392, 3328, 3232 (NH2, NH), 2176 (CN),
1
−
−
1657 (C O), 1600 (C C). H NMR (400 MHz, DMSO-d6): 9.00 (s, 1H, NH), 7.31 (d,
2H, 3JH−H = 4 Hz, CH-Ar), 7.14 (d, 2H, 3JH−H = 4 Hz, CH-Ar), 5.81 (s, 2H, NH2), 4.35
(s, 1H, CH), 2.28–1.73 (m, 6H, 3CH2).
2-Amino-5-oxo-1-phenyl-4-(p-tolyl)-1,4,5,6,7,8-hexahydroquinoline-3-carbonit
rile (10n) Yellow crystals; IR (KBr, νmax/cm−1): 3472, 3328 (NH2), 2192 (CN), 1638
1
−
−
(C O), 1590 (C C). H NMR (400 MHz, DMSO-d6): 7.61–7.11 (m, 9H, CH-Ar), 5.32
(s, 2H, NH2), 4.46 (s, 1H, CH), 2.27 (s, 3H, CH3), 2.22–1.56 (m, 6H, 3CH2).
Acknowledgements
The authors express their great appreciation to Pharmaceutics Research Center, Institute of Neu-
ropharmacology, Kerman University of Medical Sciences for supporting this investigation.

8
M. ABASZADEH AND M. SEIFI
Disclosure statement
No potential conflict of interest was reported by the authors.
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