Ammonium chloride-catalyzed four-component sonochemical synthesis of novel hexahydroquinolines bearing a sulfonamide moiety

Article abstract of DOI:10.1134/S1070428015010091

Ammonium chloride as a very inexpensive and readily available reagent efficiently catalyzes one-pot four-component condensation of dimedone with aromatic aldehyde, malononitrile or ethyl cyanoacetate, and sulfonamide derivatives in ethanol at 70°C under ultrasonic irradiation to afford the corresponding 2-amino-4-aryl-1,4,5,6,7,8-hexahydroquinolines bearing a sulfonamide moiety in high yields. In comparison to conventional methods, high yields, easy work-up, and short reaction time are advantages of this sonochemical procedure. The effects of the catalyst, solvent, and temperature are assessed.

Full text of DOI:10.1134/S1070428015010091

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 1, pp. 54–64. © Pleiades Publishing, Ltd., 2015.
Ammonium Chloride-Catalyzed Four-Component
Sonochemical Synthesis of Novel Hexahydroquinolines
Bearing a Sulfonamide Moiety*
E. M. Husseina, b
a Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, Egypt
b Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University,
Makkah 715, Saudi Arabia
e-mail: essam.hussein78@yahoo.com
Received March 29, 2014
Abstract—Ammonium chloride as a very inexpensive and readily available reagent efficiently catalyzes one-
pot four-component condensation of dimedone with aromatic aldehyde, malononitrile or ethyl cyanoacetate,
and sulfonamide derivatives in ethanol at 70°C under ultrasonic irradiation to afford the corresponding
2-amino-4-aryl-1,4,5,6,7,8-hexahydroquinolines bearing a sulfonamide moiety in high yields. In comparison to
conventional methods, high yields, easy work-up, and short reaction time are advantages of this sonochemical
procedure. The effects of the catalyst, solvent, and temperature are assessed.
DOI: 10.1134/S1070428015010091
β-Enaminones are polydentate reagents that have
wide utility in synthetic organic chemistry [1–5].
Enaminones have been employed in the preparation of
various biologically active compounds [6, 7], as well
as dye intermediates [8–11]. Sulfonamide compounds
have shown to possess several types of biological ac-
tivities [12–15], including anticancer activity [16–21].
Quinoline derivatives were found to possess several
pharmacological properties, including antibacterial
[22–24] and anticancer activities [25–30]. Multicom-
ponent reactions (MCRs) in which multiple reactions
are performed in one synthetic operation have been
used extensively to form carbon–carbon bonds in syn-
thetic chemistry [31, 32]. Such reactions offer a wide
range of possibilities for the efficient construction of
highly complex molecules in a single procedural step,
thus avoiding the complicated purification operations
and allowing savings of both solvents and reagents.
The development of cost-effective and environmental-
ly benign catalytic systems is one of the main themes
of modern organic synthesis. Ammonium chloride
(NH4Cl) is a very inexpensive, eco-friendly, and easily
available catalyst; it has been reported as catalyst for
the synthesis of various heterocyclic compounds
[33–38]. The use of ultrasound to enhance or alter
chemical reactions is called sonochemistry. The assis-
tance of ultrasonic irradiation efficiently shortens the
reaction time. Simple experimental procedure, very
high yields, increased selectivity, and clean reaction of
many ultrasound-induced organic transformations offer
additional convenience in the field of synthetic organic
chemistry [39–45]. On the other hand, the most general
synthetic approach for the synthesis of hexahydro-
quinoline derivatives having a benzenesulfonamide
moiety involves condensation of enaminones with
aldehydes and malononitrile in boiling ethanol in the
presence of triethylamine [46–50]; however, this pro-
cedure is associated with one or more disadvantages
such as the use of toxic or expensive catalyst, rela-
tively low yield, and comparatively long reaction time.
To overcome these shortcomings, as a consequence of
my interest in using MCRs for the synthesis of
N-heterocyclic compounds [51–57], I wish to report
the results obtained from a study of the synthesis of
various hexahydroquinolines 5a–5k and 6a–6k
bearing a sulfonamide moiety in the presence of
ammonium chloride as a very inexpensive and easily
available catalyst under ultrasonic irradiation in
a higher yield and in a shorter reaction time. This
synthesis involved four-component condensation of
dimedone (1), aromatic aldehyde 2a–2f, malononitrile
(3a) or ethylcyanoacetate (3b), and sulfonamide
derivative 4a or 4b in ethanol at 70°C using ammo-
* The text was submitted by the author in English.
54

AMMONIUM CHLORIDE-CATALYZED FOUR-COMPONENT SONOCHEMICAL SYNTHESIS
55
Scheme 1.
Z
O
Ar
NH2
O
O
NH4Cl (20 mol %)
EtOH, 70°C, US
S
N
O
N
+
ArCHO
+
+
CN
Z
X
Me
Me
X
O
H2N
N
S
Me
O
Me
O
1
2a–2f
3a, 3b
4a, 4b
5a–5k, 6a–6k
CN
Ar
O
O
N
X
N
S
Me
O
Me
O
7
2, Ar = Ph (a), 4-ClC6H4 (b), 4-MeC6H4 (c), 4-MeOC6H4 (d), 2-furyl (e), 4-pyridiyl (f); 3, Z = CN (a), COOEt (b); 4, X = CH2 (a),
O (b); 5, Z = CN; 6, Z = COOEt; 5, 6, X = CH2 (a–f), O (g–k); Ar = Ph (a, g), 4-ClC6H4 (b, h), 4-MeC6H4 (c, i), 4-MeOC6H4 (d, j),
2-furyl (e, k), 4-pyridiyl (f); US stands for ultrasonic irradiation.
Scheme 2.
O
O
O
O
SO2Cl
S
S
H2O, r.t.
3 min, US
Aq. HCl, 10 min
90°C, US
N
N
X
+
Ac
Ac
X
X
HN
N
N
H2N
H
H
8
9a, 9b
4a, 4b
4, 9, X = CH2 (a) O (b).
nium chloride (20 mol %) under ultrasonic irradiation,
as shown in Scheme 1 (Tables 1, 2).
methanol and ethanol ensured the formation of product
5a was in high yield and short reaction time, but the
best results (60% in 100 min) were obtained in ethanol
(Table 3, entry nos. 6, 7).
First of all, I prepared sulfonamide derivatives 4a
and 4b in short time by treatment of 4-acetamido-
benzene-1-sulfonyl chloride (8) with cyclic amines,
piperidine and morpholine, in water under ultrasonic
irradiation, followed by acid hydrolysis with aqueous
HCl under ultrasonic irradiation for 10 min
(Scheme 2).
When the reaction was performed in acetonitrile
and dioxane, the yields of the desired products were 42
and 36%, respectively (Table 3, entry nos. 1, 2). Polar
aprotic solvents such as dimethyl sulfoxide and
N,N-dimethylformamide improved the yield to 44 and
47%, respectively (Table 3, entry nos. 3, 4). Only
traces of 5a were detected in the reaction carried out in
water due to insolubility of 4a (Table 3, entry no. 5).
The reaction of dimedone (1) with benzaldehyde
(2a), malononitrile (3a), and 4-(piperidin-1-ylsulfonyl)-
aniline (4a) in the presence of ammonium chloride was
used as a model reaction to optimize the conditions.
Initially, I tried to determine the efficiencies of several
solvents chosen as reaction medium. In each case, the
substrates were mixed together with 5 mL of a solvent,
and the mixture was vigorously stirred at room tem-
perature under ultrasonic irradiation (35 kHz). Among
the tested solvents, namely acetonitrile, dioxane,
dimethyl sulfoxide, N,N-dimethylformamide, water,
methanol, and ethanol, polar protic solvents such as
To optimize the temperature conditions, the reac-
tions were carried out at different temperatures ranging
from 25 to 75°C under ultrasonic irradiation (Table 3,
entry nos. 7–11). It was observed that raising the tem-
perature to 70°C improved the yield and shortened the
reaction time (90% in 50 min; Table 3, entry no. 10).
As follows from the data in Table 3 (entry no. 11), the
yield appreciably decreased (88%) when the tempera-
ture was further raised to 75°C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

HUSSEIN
56
Table 1. Synthesis of 2-amino-4-aryl-1,4,5,6,7,8-hexahydroquinoline-3-carbonitriles 5a–5k under sonication and conven-
tional conditionsa
Sonication
Without sonication
time, min yield, %
300 65
Entry
no.
Product
Ar
X
Z
time, min
yield, %
01
02
03
04
05
06
07
08
09
10
11
5a
5b
5c
5d
5e
5f
Ph
CH2
CH2
CH2
CH2
CH2
CH2
O
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
50
40
43
38
55
60
60
52
55
50
65
90
92
92
95
87
81
89
94
92
96
84
4-ClC6H4
4-MeC6H4
4-MeOC6H4
2-Furyl
210
230
200
300
300
300
270
300
240
300
67
62
70
60
57
60
61
60
65
60
4-Pyridyl
Ph
5g
5h
5i
4-ClC6H4
4-MeC6H4
4-MeOC6H4
2-Furyl
O
O
5j
O
5k
O
a
Hereinafter: reaction conditions: 1–4, 1 mmol each; NH4Cl, 0.2 mmol (20 mol %); ethanol, 5 mL; 70ºC; ultrasonic irradiation at 35 kHz.
Yields of isolated products are given.
Table 2. Synthesis of ethyl 2-amino-4-aryl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylates 6a–6k under sonication and con-
ventional conditions
Sonication
Without sonication
time, min yield, %
360 56
Entry
no.
Product
no.
Ar
X
Z
time, min
yield, %
01
02
03
04
05
06
07
08
09
10
11
6a
6b
6c
6d
6e
6f
Ph
CH2
CH2
CH2
CH2
CH2
CH2
O
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
60
45
45
40
60
65
65
50
56
54
65
88
90
91
94
85
80
85
91
90
93
82
4-ClC6H4
4-MeC6H4
4-MeOC6H4
2-Furyl
300
300
280
360
360
360
280
300
280
360
60
60
62
60
59
52
60
57
60
53
4-Pyridyl
Ph
6g
6h
6i
4-ClC6H4
4-MeC6H4
4-MeOC6H4
2-Furyl
O
O
6j
O
6k
O
Different catalysts were also tested. No desired
product was detected in the absence of any catalyst
(Table 4, entry no. 1). Acid catalysts such as acetic
acid and p-toluenesulfonic acid can push the reaction
toward the formation of product 5a in yields of 45 and
43%, respectively (Table 4, entry nos. 2, 3). The yield
was improved to 69 and 70% when basic catalysts
such as triethylamine and piperidine were used
(Table 4, entry nos. 4, 5).
chloride, compound 5a was isolated in good yields
(Table 4, entry nos. 6–8). The best results (yield 90%)
were obtained when ammonium chloride was used
(Table 4, entry no. 8). To determine the appropriate
concentration of the catalyst, the model reaction was
carried out at different concentrations of ammonium
chloride such as 5, 10, 15, 20, and 25 mol %. The
product was formed in 59, 76, 83, 90, and 90% yield,
respectively (Table 5). This indicated that 20 mol % of
ammonium chloride is sufficient to carry out the
reaction smoothly.
In the presence of ammonium salts such as ammo-
nium acetate, ammonium carbonate, and ammonium
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

AMMONIUM CHLORIDE-CATALYZED FOUR-COMPONENT SONOCHEMICAL SYNTHESIS
57
Table 3. Synthesis of 2-amino-7,7-dimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (5a) in different
solvents (5 mL) at different temperatures
With sonication
Without sonication
Entry no.
Solvent
Temperature, °C
time, min
yield, %
time, min
yield, %
01
02
03
04
05
06
07
08
09
10
11
Acetonitrile
Dioxane
DMSO
25
25
25
25
25
25
25
50
60
70
75
300
300
240
180
360
120
100
090
075
050
050
42
36
300
300
240
180
360
120
100
090
075
050
050
20
18
25
30
–
44
DMF
47
Water
Traces
51
Methanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
37
40
42
52
61
64
60
69
83
90
88
To assess the generality of the optimized reaction
conditions (ethanol, 70°C, 20 mol % NH4Cl), dime-
done was brought into four-component cyclocondensa-
tion with several aromatic aldehydes 2a–2f, malono-
nitrile (3a), and 4-(piperidin-1-ylsulfonyl)aniline (4a)
or 4-(morpholin-1-ylsulfonyl)aniline (4b). As a result,
the corresponding 2-amino-4-aryl-1,4,5,6,7,8-hexahy-
droquinoline-3-carbonitriles 5a–5k were formed in
81–95% yield (Scheme 1). When ethyl cyanoacetate
(3b) was used instead of malononitrile (3a), ethyl
2-amino-4-aryl-1,4,5,6,7,8-hexahydroquinoline-3-car-
boxylates 6a–6k were obtained rather than the expect-
ed 4-aryl-1,2,5,6,7,8-hexahydroquinoline-3-carbo-
nitriles 7 (Scheme 1). Analogous reactions under con-
ventional conditions gave much lower yields and took
longer reaction time than did the corresponding reac-
tions under ultrasonic irradiation (Tables 1 and 2).
Table 4. Effect of catalyst on the yield of of 2-amino-7,7-
dimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-
carbonitrile (5a) under ultrasonic irradiationa
Entry no.
Catalyst
Time, min
Yield, %
1
2
3
4
5
6
7
8
None
360
360
360
300
300
120
200
050
–
AcOH
45
43
69
70
72
65
90
TsOH
Et3N
The structure of the isolated new products 5a–5k
and 6a–6k was determined by analyzing their physical
Piperidine
NH4OAc
(NH4)2CO3
NH4Cl
1
and spectroscopic data, including IR, H NMR, and
13C NMR spectra. For example, compound 5b showed
in the IR spectrum strong absorption bands at 3435 and
3361 cm–1 due to the amino group and very strong ab-
sorption bands at 2191 and 1665 cm–1 due to the cyano
a
Ethanol, 5 mL; 70°C; amount of catalyst 20 mol %.
1
and carbonyl groups, respectively. The H NMR spec-
Table 5. Catalytic activity of ammonium chloride in the
synthesis of 5a under ultrasonic irradiationa
trum displayed two multiplets at δ 0.94–0.99 and 1.04–
1.21 ppm for two methyl and three methylene (piperi-
dinyl) groups, as well as three singlets at δ 1.37, 4.13,
and 7.23 ppm from protons of the two methylene (cy-
clohexene ring), methine, and amino groups, respec-
tively. In the 13C NMR spectrum of 5b, the nitrile
and carbonyl carbons characteristically appeared at
δC 119.88 and 195.75 ppm, respectively.
Entry
no.
Amount of NH4Cl,
mol %
Time, min
Yield, %
1
2
3
4
5
05
10
15
20
25
120
090
060
050
050
59
76
83
90
90
The IR spectrum of 6a contained two strong ab-
sorption bands at 3436 and 3361 cm–1 (NH2) and two
absorption bands at 1670 and 1640 cm–1 (C=O), while
a
Ethanol, 5 mL; 70 ºC.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

HUSSEIN
58
Scheme 3.
O
O
O
Cl–
H
NH3
–NH4Cl
–H2O
Me
Me
Me
Me
OH
R
Me
Me
O
NHR
N
··
H
H2N
R
H
A
O
H
NH3
OH
Z
CN
Ar
H
H
Ar
··
Ar
H
–HCl
–NH4
–OH–
NH3
CN
H
CN
Cl–
Z
B
Z
O
Ar
O
Ar
O
Ar
Z
Z
Z
A
+ B
Me
Me
Me
Me
Me
Me
··
NH
N
R
NH
N
R
NH2
N
R
5, 6
X
R =
; X = CH2, O; 5, Z = CN; 6, Z = COOEt.
N
S
O
O
no band assignable to cyano group was observed. In
the 1H NMR spectrum of 6a, two signals at δ 1.20 and
4.28 ppm were present due to protons in the ester ethyl
group. In the 13C NMR spectrum, the two carbonyl
carbons resonated at δC 162.54 and 195.72 ppm.
pensive, easily available, and neutral catalyst and over-
comes shortcoming of the previously reported syn-
thetic approach for the synthesis of hexahydro-
quinolines.
EXPERIMENTAL
I have not established an exact mechanism for the
formation of 2-amino-4-aryl-1,4,5,6,7,8-hexahydro-
quinolines 5a–5k and 6a–6k; however, a probable
mechanism is shown in Scheme 3. The condensation
of dimedone (1) with sulfonamide derivative 4 gives
enaminone intermediate A, while Knoevenagel con-
densation of aromatic aldehyde 2 with CH acid 3 leads
to arylmethylidene intermediate B. The latter acts as
Michael acceptor, and the reaction proceeds via
domino Knoevenagel cyclocondensation. Enaminone
A adds to arylmethylidene intermediate B, and intra-
molecular cyclization of the resulting adduct yields
final 2-amino-4-aryl-1,4,5,6,7,8-hexahydroquinoline
derivative 5 or 6.
The progress of reactions was monitored by TLC.
All melting points were measured on a Gallenkamp
apparatus. The IR spectra were recorded in KBr on
1
a Shimadzu 470 IR spectrometer (Japan). The H and
13C NMR spectra were measured on a Varian EM-200
spectrometer (USA) at 400 MHz and 100 MHz, re-
spectively, using tetramethylsilane as internal standard
and DMSO-d6 as solvent. The mass spectra were deter-
mined on a JEOL JMS-600 spectrometer (Japan). The
elemental analyses were obtained on a VarioEL V2.3
analyzer. Ultrasonication was performed in an Elma
Hans Schmidbauer D-7700 ultrasonic cleaner
(Germany) with a frequency of 35 kHz. The reaction
flasks were immersed in every part of the cleaner in
such a way that the surface of the reaction mixture was
slightly lower than the water level in the cleaner, and
the temperature of the water bath was controlled using
an electronic temperature control system. Compounds
1, 2a–2f, 3a, 3b, and 8 were commercial products.
In conclusion, I have developed an economic and
environmentally friendly procedure for the synthesis of
2-amino-4-aryl-1,4,5,6,7,8-hexahydroquinolines
bearing sulfonamide moiety in a higher yield and in
a shorter reaction time. The developed procedure
involves the use of ammonium chloride as a very inex-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

AMMONIUM CHLORIDE-CATALYZED FOUR-COMPONENT SONOCHEMICAL SYNTHESIS
59
1
4-(Piperidin-1-ylsulfonyl)aniline (4a). Piperidine,
10 mmol, was added to a suspension of 10 mmol of
4-acetamidobenzene-1-sulfonyl chloride) in 20 mL of
distilled water. The mixture was sonicated for 3 min at
room temperature until a pasty material appeared. The
product was collected by filtration and transferred to
a flask, 5 mL of concentrated aqueous HCl diluted
with 10 mL of water was added, and the mixture was
sonicated for 10 min at 90°C. The solution was cooled
and filtered, the filtrate was made alkaline (litmus) by
cautiously adding 10% aqueous sodium carbonate
under stirring and thoroughly cooled with ice, and the
granular white precipitate was collected by filtration,
washed with distilled water, and recrystallized from
ethanol. Compound 4a was isolated as white powder in
94% yield. The properties of the product were con-
sistent with published data [58].
(SO2). H NMR spectrum, δ, ppm: 0.94 s (6H, CH3),
1.00–1.18 m (6H, CH2), 1.29 s (4H, CH2), 1.56 t (4H,
CH2), 4.12 s (1H, CH), 6.64 d (2H, CH), 6.61–6.94 m
(7H, Ph, NH2), 7.11 d (2H, CH). C NMR spectrum,
13
δC, ppm: 23.01 (2C, CH3), 24.67 (CH2), 31.80, 35.02,
45.65 (C4), 46.59 (2C, CH2), 49.91 (2C, CH2), 112.62
(CH), 112.70 (2C, CH), 119.90 (CN), 127.16 (2C,
CH), 129.41 (2C, CH), 129.47 (2C, CH), 143.71 (2C),
153.03 (2C), 158.51, 162.60, 195.70 (C=O). Mass
spectrum (EI), m/z (Irel, %): 515.97 (18) [M]+, 361.09
(100). Found, %: C 67.24; H 6.05; N 10.67; S 6.00.
C29H32N4O3S. Calculated, %: C 67.42; H 6.24;
N 10.84; S 6.21. M 516.22.
2-Amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-
1-[4-(piperidin-1-ylsulfonyl)phenyl]-1,4,5,6,7,8-
hexahydroquinoline-3-carbonitrile (5b). Pale yellow
needles, mp 132–134°C. IR spectrum, ν, cm–1: 3435,
3361 (NH2), 3254 (sec. SO2N), 3095 (C–Harom), 2950
(C–Haliph), 2191 (C≡N), 1665 (C=O), 1308, 1142
4-(Morpholin-4-ylsulfonyl)aniline (4b) was syn-
thesized in a similar way [58].
1
(SO2). H NMR spectrum, δ, ppm: 0.94–0.99 s (6H,
Typical silent procedure for the synthesis of
2-amino-4-aryl-1,4,5,6,7,8-hexahydroquinolines 5a–
5k and 6a–6k. A 50-mL flask was charged with
0.140 g (1 mmol) of dimedone (1), 0.066 g (1 mmol)
of malononitrile (3a) or ethyl cyanoacetate (3b),
1 mmol of 4-(piperidin-1-ylsulfonyl)aniline (4a) or
4-(morpholin-4-ylsulfonyl)aniline (4b), 1 mmol of
aromatic aldehyde 2a–2f, and 0.0106 g (20 mol %) of
ammonium chloride in 5 mL of ethanol. The mixture
was stirred at 70°C until the reaction was complete
(TLC), and the solid product was collected by filtra-
tion, washed with cold water to remove excess ammo-
nium chloride, and recrystallized from ethanol.
CH3), 1.04–1.21 m (6H, CH2), 1.37 s (4H, CH2), 1.60 t
(4H, CH2), 4.13 s (1H, CH), 6.66 d (2H, CH), 7.14 d
(2H, CH), 7.23 s (2H, NH2, D2O-exchangeable), 7.33 d
(2H, CH), 7.49 d (2H, CH). 13C NMR spectrum, δC,
ppm: 23.03 (2C, CH3), 24.69 (3C, CH2), 31.85, 35.11,
45.67 (C4), 46.61 (2C, CH2), 49.93 (2C, CH2), 112.67
(2C, CH), 119.88 (CN), 128.32 (2C, CH), 129.16 (3C),
129.46 (2C, CH), 131.13 (2C, CH), 143.79, 153.05,
158.60, 162.68, 195.75 (C=O). Mass spectrum (EI),
m/z (Irel, %): 549.35 (26) [M]+, 515.02 (62), 361.28
(100). Found, %: C 62.92; H 5.46; Cl 6.13; N 10.00;
S 5.60. C29H31ClN4O3S. Calculated, %: C 63.20;
H 5.67; Cl 6.43; N 10.17; S 5.82. M 550.18.
Typical sonochemical procedure for the syn-
thesis of 2-amino-4-aryl-1,4,5,6,7,8-hexahydro-
quinolines. A 50-mL flask was charged with 0.140 g
(1 mmol) of dimedone (1), 1 mmol of malononitrile
(3a) or ethyl cyanoacetate (3b), 1 mmol of 4-(piper-
idin-1-ylsulfonyl)aniline (4a) or 4-(morpholin-4-ylsul-
fonyl)aniline (4b), 1 mmol of aromatic aldehyde 2a–
2f, and 0.0106 g (20 mol %) of ammonium chloride in
5 mL of ethanol. The mixture was sonicated at 70°C
for a time indicated in Table 1 or 2 (TLC monitoring).
When the reaction was complete, the precipitate was
filtered off, washed with cold water to remove excess
ammonium chloride, and recrystallized from ethanol.
2-Amino-7,7-dimethyl-4-(4-methylphenyl)-5-
oxo-1-[4-(piperidin-1-ylsulfonyl)phenyl]-1,4,5,6,7,8-
hexahydroquinoline-3-carbonitrile (5c). Pale yellow
needles; mp 156–157°C. IR spectrum, ν, cm–1: 3436,
3361 (NH2), 3256 (sec. SO2N), 3050 (C–Harom), 2950
(C–Haliph), 2195 (C≡N), 1640 (C=O), 1308, 1153
1
(SO2). H NMR spectrum, δ, ppm: 0.98 s (6H, CH3),
1.34 s (2H, CH2), 1.52–1.54 m (4H, CH2), 2.09–2.15 m
(2H, CH2), 2.28 s (2H, CH2), 2.73 s (3H, CH3), 3.42 t
(4H, CH2), 4.60 s (1H, CH), 5.66 s (2H, NH2, D2O-
exchangeable), 6.61 d (2H, CH), 6.71 d (2H, CH),
7.10 d (2H, CH), 7.30 d (2H, CH). Mass spectrum
(EI), m/z (Irel, %): 529.92 (35) [M]+, 140.56 (100).
Found, %: C 67.68; H 6.30; N 10.54; S 5.86.
C30H34N4O3S. Calculated, %: C 67.90; H 6.46;
N 10.56; S 6.04. M 530.24.
2-Amino-7,7-dimethyl-5-oxo-4-phenyl-1-[4-(pi-
peridin-1-ylsulfonyl)phenyl]-1,4,5,6,7,8-hexahydro-
quinoline-3-carbonitrile (5a). Pale yellow needles,
mp 148–151°C. IR spectrum, ν, cm–1: 3436, 3362
(NH2), 3256 (sec. SO2N), 3076 (C–Harom), 2950
(C–Haliph), 2199 (C≡N), 1659 (C=O), 1308, 1153
2-Amino-4-(4-methoxyphenyl)-7,7-dimethyl-5-
oxo-1-[4-(piperidin-1-ylsulfonyl)phenyl]-1,4,5,6,7,8-
hexahydroquinoline-3-carbonitrile (5d). Pale yellow
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60
crystals, mp 138–140°C. IR spectrum, ν, cm–1: 3435,
3362 (NH2), 3255 (sec. SO2N), 3090 (C–Harom), 2960
(C–Haliph), 2187 (C≡N), 1665 (C=O), 1308, 1150
quinoline-3-carbonitrile (5g). Pale yellow needles,
mp 212–214°C. IR spectrum, ν, cm–1: 3443, 3365
(NH2), 3250 (sec. SO2N), 3080 (C–Harom), 2984
(C–Haliph), 2220 (C≡N), 1643 (C=O), 1315, 1151
1
(SO2). H NMR spectrum, δ, ppm: 0.94 s (3H, CH3),
1
1.06 s (3H, CH3), 1.37 s (2H, CH2), 1.58–1.59 m (4H,
CH2), 2.12–2.26 m (2H, CH2), 2.39 s (2H, CH2), 3.72 t
(4H, CH2), 3.87 s (3H, OCH3), 4.15 s (2H, NH2, D2O-
exchangeable), 4.60 s (1H, CH), 6.65 d (2H, CH),
6.78 d (2H, CH), 7.11 d (2H, CH), 7.47 d (2H, CH).
Mass spectrum (EI), m/z (Irel, %): 546.05 (31) [M]+,
256.17 (100). Found, %: C 65.70; H 6.01; N 10.00;
S 5.62. C30H34N4O4S. Calculated, %: C 65.91; H 6.27;
N 10.25; S 5.87. M 546.23.
(SO2). H NMR spectrum, δ, ppm: 0.94 s (6H, CH3),
1.84 s (2H, CH2), 1.92 t (4H, CH2), 2.16 s (2H, CH2),
2.41 t (4H, CH2), 4.15 s (1H, CH), 6.60 d (2H, CH),
6.76–7.09 m (5H, Ph), 7.19 s (2H, NH2, D2O-ex-
changeable), 7.26 d (2H, CH). Mass spectrum (EI), m/z
(Irel, %): 518.00 (29) [M]+, 362.79 (100). Found, %:
C 64.66; H 5.59; N 10.61; S 5.90. C28H30N4O4S. Cal-
culated, %: C 64.84; H 5.83; N 10.80; S 6.18. M 518.63.
2-Amino-4-(4-chlorophenyl)-7,7-dimethyl-
1-[4-(morpholin-4-ylsulfonyl)phenyl]-5-oxo-
1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (5h).
Pale yellow crystals, mp 209–210°C. IR spectrum, ν,
cm–1: 3443, 3365 (NH2), 3255 (sec. SO2N), 3037
(C–Harom), 2984 (C–Haliph), 2231 (C≡N), 1643 (C=O),
2-Amino-4-(furan-2-yl)-7,7-dimethyl-5-oxo-
1-[4-(piperidin-1-ylsulfonyl)phenyl]-1,4,5,6,7,8-
hexahydroquinoline-3-carbonitrile (5e). Pale yellow
crystals, mp 158–159°C. IR spectrum, ν, cm–1: 3430,
3362 (NH2), 3250 (sec. SO2N), 3054 (C–Harom), 2949
(C–Haliph), 2197 (C≡N), 1682 (C=O), 1308, 1145
1
1316, 1152 (SO2). H NMR spectrum, δ, ppm: 0.94 s
1
(SO2). H NMR spectrum, δ, ppm: 1.04 s (3H, CH3),
(6H, CH3), 1.86 s (2H, CH2), 1.98 t (4H, CH2), 2.19 s
(2H, CH2), 2.54 t (4H, CH2), 4.19 s (1H, CH), 6.69 d
(2H, CH), 7.21 d (2H, CH), 7.36 d (2H, CH), 7.45 d
(2H, CH), 7.89 s (2H, NH2, D2O-exchangeable). Mass
spectrum (EI), m/z (Irel, %): 552.81 (25) [M]+, 516.01
(7), 362.94 (100). Found, %: C 60.55; H 5.00; Cl 6.20;
N 10.00; S 5.59. C28H29ClN4O4S. Calculated, %:
C 60.81; H 5.29; Cl 6.41; N 10.13; S 5.80. M 553.07.
1.09 s (3H, CH3), 1.38 m (2H, CH2), 1.60 m (4H,
CH2), 2.25 s (2H, CH2), 2.41 s (2H, CH2), 4.17 s (2H,
NH2, D2O-exchangeable), 4.54 s (1H, CH), 4.72 t (4H,
CH2), 6.14 t (1H, CH), 6.24 d (1H, CH), 6.67 d (2H,
CH), 7.24 d (1H, CH), 7.49 d (2H, CH). 13C NMR
spectrum, δC, ppm: 23.08 (2C, CH3), 25.51 (3C, CH2),
33.10, 36.14, 45.23 (C4), 46.88 (2C, CH2), 49.71 (2C,
CH2), 111.62 (CH), 114.70 (CH), 119.74 (CN), 127.30
(2C, CH), 130.30 (CH), 129.47 (2C, CH), 143.71 (2C),
153.01 (2C), 157.22, 160.50, 196.70 (C=O). Mass
spectrum (EI), m/z (Irel, %): 505.77 (15) [M]+, 361.28
(100). Found, %: C 63.80; H 5.74; N 10.84; S 6.09.
C27H30N4O4S. Calculated, %: C 64.01; H 5.97;
N 11.06; S 6.33. M 506.20.
2-Amino-7,7-dimethyl-4-(4-methylphenyl)-
1-[4-(morpholin-4-ylsulfonyl)phenyl]-5-oxo-
1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (5i).
Pale yellow crystal, mp 218–220°C. IR spectrum, ν,
cm–1: 3442, 3361 (NH2), 3260 (sec. SO2N), 3090
(C–Harom), 2984 (C–Haliph), 2194 (C≡N), 1643 (C=O),
1
1316, 1160 (SO2). H NMR spectrum, δ, ppm: 0.93 s
(6H, CH3), 1.82 s (2H, CH2), 1.92 t (4H, CH2), 2.15 s
(2H, CH2), 2.47 s (3H, CH3), 2.58 t (4H, CH2), 4.11 s
(1H, CH), 6.66 d (2H, CH), 7.18 d (2H, CH), 7.30 d
(2H, CH), 7.39 d (2H, CH), 7.92 s (2H, NH2, D2O-ex-
2-Amino-7,7-dimethyl-5-oxo-1-[4-(piperidin-
1-ylsulfonyl)phenyl]-4-(pyridin-4-yl)-1,4,5,6,7,8-
hexahydroquinoline-3-carbonitrile (5f). Pale yellow
crystals; mp 164–165°C. IR spectrum, ν, cm–1: 3436,
3361 (NH2), 3250 (sec. SO2N), 3095 (C–Harom), 2950
(C–Haliph), 2200 (C≡N), 1640 (C=O), 1308, 1154
13
changeable). C NMR spectrum, δC, ppm: 22.53 (2C,
CH3), 24.01 (CH3), 28.69 (2C, CH2), 32.34, 35.80,
45.91 (C4), 47.52 (2C, CH2), 50.12 (2C, CH2), 111.57
(2C, CH), 119.49 (CN), 128.30 (2C, CH), 129.20 (3C),
129.45 (2C, CH), 131.11 (2C, CH), 143.78, 153.15,
158.62, 162.66, 195.38 (C=O). Mass spectrum (EI),
m/z (Irel, %): 532.82 (11) [M]+, 240.92 (53), 229.85
(82), 173.92 (100). Found, %: C 65.12; H 5.84;
N 10.22; S 5.79. C29H32N4O4S. Calculated, %:
C 65.39; H 6.06; N 10.52; S 6.02. M 532.65.
1
(SO2). H NMR spectrum, δ, ppm: 0.93 s (6H, CH3),
1.01–1.20 m (6H, CH2), 1.35 s (4H, CH2), 2.43 t (4H,
CH2), 4.16 s (1H, CH), 6.65 d (2H, CH), 7.11 d (2H,
CH), 7.27 s (2H, NH2, D2O-exchangeable), 7.35 d (2H,
CH), 7.52 d (2H, CH). Mass spectrum (EI), m/z
(Irel, %): 517.05 (14) [M]+, 228.32 (100). Found, %:
C 64.69; H 5.85; N 13.04; S 5.90. C28H31N5O3S. Cal-
culated, %: C 64.97; H 6.04; N 13.53; S 6.19. M 517.64.
2-Amino-4-(4-methoxyphenyl)-7,7-dimethyl-
1-[4-(morpholin-4-ylsulfonyl)phenyl]-5-oxo-
2-Amino-7,7-dimethyl-1-[4-(morpholin-4-ylsul-
fonyl)phenyl]-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydro-
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AMMONIUM CHLORIDE-CATALYZED FOUR-COMPONENT SONOCHEMICAL SYNTHESIS
61
119.88, 126.59 (2C, CH), 127.17 (2C, CH), 128.37,
129.44 (2C, CH), 144.79, 153.05, 158.50, 162.54
(C=O), 195.72 (C=O). Mass spectrum (EI), m/z
(Irel, %): 562.91 (19) [M]+, 533.26 (27), 506.01 (46),
139.88 (100). Found, %: C 65.82; H 6.40; N 7.12;
S 5.50. C31H37N3O5S. Calculated, %: C 66.05; H 6.62;
N 7.45; S 5.69. M 563.71.
1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (5j).
Pale yellow crystals, mp 180–182°C. IR spectrum, ν,
cm–1: 3443, 3364 (NH2), 3250 (sec. SO2N), 3095
(C–Harom), 2984 (C–Haliph), 2222 (C≡N), 1644 (C=O),
1
1316, 1153 (SO2). H NMR spectrum, δ, ppm: 0.95 s
(3H, CH3), 0.96 s (3H, CH3), 1.86 s (2H, CH2), 1.99 t
(4H, CH2), 2.22 s (2H, CH2), 3.29 t (4H, CH2), 4.07 s
(3H, OCH3), 4.25 s (1H, CH), 6.91 d (2H, CH), 7.24 d
(2H, CH), 7.35 d (2H, CH), 7.47 d (2H, CH), 8.13 s
(2H, NH2, D2O-exchangeable). 13C NMR spectrum, δC,
ppm: 22.61 (2C, CH3), 28.72 (2C, CH2), 32.69, 36.91,
45.82 (C4), 47.67 (2C, CH2), 51.24 (CH3), 52.46 (2C,
CH2), 112.52 (2C, CH), 120.61 (CN), 128.30 (2C,
CH), 129.91 (3C), 130.65 (2C, CH), 131.44 (2C, CH),
143.70, 153.15, 158.61, 162.58, 197.02 (C=O). Mass
spectrum (EI), m/z (Irel, %): 548.89 (16) [M]+, 363.67
(100). Found, %: C 63.10; H 5.60; N 9.98; S 5.70.
C29H32N4O5S. Calculated, %: C 63.48; H 5.88;
N 10.21; S 5.84. M 548.65.
Ethyl 2-amino-4-(4-chlorophenyl)-7,7-dimethyl-
5-oxo-1-[4-(piperidin-1-ylsulfonyl)phenyl]-
1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (6b).
Pale yellow crystals, mp 147–148°C. IR spectrum, ν,
cm–1: 3436, 3361 (NH2), 3255 (sec. SO2N), 3085
(C–Harom), 2956 (C–Haliph), 1695 (C=O), 1640 (C=O),
1
1308, 1153 (SO2). H NMR spectrum, δ, ppm: 0.93 s
(6H, CH3), 1.06–1.11 m (2H, CH2), 1.38 t (3H, CH3),
1.59–1.60 m (4H, CH2), 2.14 s (2H, CH2), 2.39 s (2H,
CH2), 2.91 t (4H, CH2), 3.99 br.s (2H, NH2, D2O-ex-
changeable), 4.36 q (2H, OCH2), 4.63 s (1H, CH),
6.66 d (2H, CH), 7.15 d (2H, CH), 7.23 d (2H, CH),
7.49 d (2H, CH). Mass spectrum (EI), m/z (Irel, %):
597.01 (22) [M]+, 562.11 (46), 139.26 (100). Found,
%: C 62.01; H 6.00; Cl 5.68; N 6.80; S 5.10.
C31H36ClN3O5S. Calculated, %: C 62.25; H 6.07;
Cl 5.93; N 7.02; S 5.36. M 598.15.
2-Amino-4-(furan-2-yl)-7,7-dimethyl-1-[4-(mor-
pholin-4-ylsulfonyl)phenyl]-5-oxo-1,4,5,6,7,8-hexa-
hydroquinoline-3-carbonitrile (5k). Pale yellow
crystals, mp 216–218°C. IR spectrum, ν, cm–1: 3440,
3396 (NH2), 3255 (sec. SO2N), 3080 (C–Harom), 2990
(C–Haliph), 2196 (C≡N), 1660 (C=O), 1308, 1145
Ethyl 2-amino-7,7-dimethyl-4-(4-methylphenyl)-
5-oxo-1-[4-(piperidin-1-ylsulfonyl)phenyl]-
1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (6c).
Pale yellow needles, mp 144–146°C. IR spectrum, ν,
cm–1: 3436, 3361 (NH2), 3256 (sec. SO2N), 3095
(C–Harom), 2949 (C–Haliph), 1723 (C=O), 1640 (C=O),
1
(SO2). H NMR spectrum, δ, ppm: 1.00 s (3H, CH3),
1.08 s (3H, CH3), 1.92 t (4H, CH2), 2.28 s (2H, CH2),
2.71 s (2H, CH2), 4.10 t (4H, CH2), 4.42 s (1H,
CH), 5.03 s (2H, NH2, D2O-exchaneable), 6.15 t (1H,
CH), 6.23 d (1H, CH), 6.71 d (2H, CH), 7.28 d (1H,
CH), 7.55 d (2H, CH). Mass spectrum (EI), m/z
(Irel, %): 507.81 (39) [M]+, 216.87 (100). Found:
C 61.21; H 5.25; N 10.80; S 6.02. C26H28N4O5S. Cal-
culated, %: C 61.40; H 5.55; N 11.02; S 6.30. M 508.59.
1
1308, 1153 (SO2). H NMR spectrum, δ, ppm: 0.89 s
(6H, CH3), 1.03–1.09 m (2H, CH2), 1.14 t (3H, CH3),
1.55–1.56 m (4H, CH2), 2.18 s (2H, CH2), 2.36 s (3H,
CH3), 2.40 s (2H, CH2), 2.85 t (4H, CH2), 4.10 br.s
(2H, NH2, D2O-exchangeable), 4.30 q (2H, OCH2),
4.58 s (1H, CH), 6.61 d (2H, CH), 7.23 d (2H, CH),
7.43 d (2H, CH), 7.82 d (2H, CH). 13C NMR spectrum,
δC, ppm: 14.03 (CH3), 21.33 (CH3), 23.01 (2C, CH3),
24.67 (2C, CH2), 31.88 (2C, CH2), 40.13, 46.59 (3C,
CH2), 62.29 (C4), 101.14, 112.64 (2C, CH), 115.85,
119.91, 128.71, 129.42, 129.95 (2C, CH), 130.00 (2C,
CH), 131.00 (2C, CH), 143.49, 144.45, 153.03, 154.99,
162.03 (C=O), 193.98 (C=O). Mass spectrum (EI), m/z
(Irel, %): 576.96 (13) [M]+, 361.50 (100). Found, %:
C 66.30; H 6.56; N 7.00; S 5.39. C32H39N3O5S. Calcu-
lated, %: C 66.53; H 6.80; N 7.27; S 5.55. M 577.73.
Ethyl 2-amino-7,7-dimethyl-5-oxo-4-phenyl-
1-[4-(piperidin-1-ylsulfonyl)phenyl]-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (6a). Pale yellow
needles, mp 157–158°C. IR spectrum, ν, cm–1: 3436,
3361 (NH2), 3255 (sec. SO2N), 3095 (C–Harom), 2950
(C–Haliph), 1691 (C=O), 1640 (C=O), 1308, 1153
1
(SO2). H NMR spectrum, δ, ppm: 0.94 s (6H, CH3),
1.06–1.11 m (2H, CH2), 1.20 t (3H, CH3), 1.59–1.61 m
(4H, CH2), 2.36 s (2H, CH2), 2.40 s (2H, CH2), 2.85 t
(4H, CH2), 4.00 br (2H, NH2, D2O-exchangeable),
4.28 q (2H, OCH2), 4.66 s (1H, CH), 6.67 d (2H, CH),
7.15–7.24 m (5H, Ph), 7.67 d (2H, CH). 13C NMR
spectrum, δC, ppm: 23.03 (CH3), 24.69 (2C, CH3),
26.81 (CH2), 28.43 (2C, CH2), 31.85, 35.55, 35.70
(C4), 45.77 (CH2), 46.61 (2C, CH2), 49.98 (CH2),
58.27 (CH2), 112.64 (CH), 112.69 (2C, CH), 119.80,
Ethyl 2-amino-4-(4-methoxyphenyl)-7,7-di-
methyl-5-oxo-1-[4-(piperidin-1-ylsulfonyl)phenyl]-
1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (6d).
Pale yellow crystals, mp 165–166°C. IR spectrum, ν,
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cm–1: 3436, 3361 (NH2), 3254 (sec. SO2N), 3090
(C–Harom), 2949 (C–Haliph), 1690 (C=O), 1640 (C=O),
1308, 1153 (SO2). 1H NMR spectrum, δ, ppm: 0.93 s
(6H, CH3), 1.14 t (3H, CH3), 1.35 s (2H, CH2), 1.36–
1.39 m (2H, CH2), 1.59–1.62 m (4H, CH2), 2.91 t (4H,
CH2), 3.74 s (2H, CH2), 3.86 s (3H, OCH3), 4.00 br.s
(2H, NH2, D2O-exchangeable), 3.34 q (2H, OCH2),
4.61 s (1H, CH), 6.66 d (4H, CH), 7.49 d (4H, CH).
Mass spectrum (EI), m/z (Irel, %): 592.72 (10) [M]+,
275.00 (100). Found, %: C 64.50; H 6.39; N 6.90;
S 5.11. C32H39N3O6S. Calculated, %: C 64.73; H 6.62;
N 7.08; S 5.40. M 593.26.
1.10 t (3H, CH3), 1.79 s (2H, CH2), 1.90 t (4H, CH2),
2.11 s (2H, CH2), 2.40 t (4H, CH2), 4.15 s (1H, CH),
4.28 q (2H, OCH2), 4.92 br.s (2H, NH2, D2O-ex-
changeable), 6.64 d (2H, CH), 6.65–6.90 m (5H, Ph),
7.26 d (2H, CH). Mass spectrum (EI), m/z (Irel, %):
564.91 (12) [M]+, 362.91 (100). Found, %: C 63.50;
H 6.00; N 7.14; S 5.50. C30H35N3O6S. Calculated, %:
C 63.70; H 6.24; N 7.43; S 5.67. M 565.68.
Ethyl 2-amino-4-(4-chlorophenyl)-7,7-dimethyl-
1-[4-(morpholin-4-ylsulfonyl)phenyl]-5-oxo-
1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (6h).
Pale yellow needles, mp 172–173°C. IR spectrum, ν,
cm–1: 3443, 3359 (NH2), 3251 (sec. SO2N), 3054
(C–Harom), 2952 (C–Haliph), 1722 (C=O), 1643 (C=O),
Ethyl 2-amino-4-(furan-2-yl)-7,7-dimethyl-5-
oxo-1-[4-(piperidin-1-ylsulfonyl)phenyl]-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (6e). Pale yellow
crystals, mp 159–161°C. IR spectrum, ν, cm–1: 3436,
3362 (NH2), 3252 (sec. SO2N), 3037 (C–Harom), 2950
(C–Haliph), 1692 (C=O), 1640 (C=O), 1308, 1153
1
1316, 1156 (SO2). H NMR spectrum, δ, ppm: 0.94 s
(3H, CH3), 1.06 s (3H, CH3), 1.17 t (3H, CH3), 1.37 t
(4H, CH2), 2.18 s (2H, CH2), 2.41 s (2H, CH2), 2.89 t
(4H, CH2), 3.71 s (1H, CH), 4.17 br.s (2H, NH2, D2O-
exchangeable), 4.35 q (2H, OCH2), 6.68 d (2H, CH),
7.28 d (2H, CH), 7.49 d (2H, CH), 7.88 d (2H, CH).
Mass spectrum (EI), m/z (Irel, %): 599.18 (15) [M]+,
279.56 (100). Found, %: C 59.81; H 5.60; Cl 5.64;
N 7.10; S 5.16. C30H34ClN3O6S. Calculated, %:
C 60.04; H 5.71; Cl 5.91; N 7.00; S 5.34. M 600.13.
1
(SO2). H NMR spectrum, δ, ppm: 1.02 s (6H, CH3),
1.32 t (3H, CH3), 1.40 m (2H, CH2), 1.55 m (4H, CH2),
2.21 s (2H, CH2), 2.94 s (2H, CH2), 3.70 t (4H, CH2),
3.80 s (1H, CH), 4.20 br.s (2H, NH2, D2O-exchange-
able), 4.31 q (2H, OCH2), 6.67 d (2H, CH), 7.34 t (1H,
CH), 7.50 d (2H, CH), 7.66 d (1H, CH), 7.94 d (1H,
CH). Mass spectrum (EI), m/z (Irel, %): 553.01 (20)
[M]+, 216.00 (100). Found, %: C 62.68; H 6.09;
N 7.41; S 5.52. C29H35N3O6S. Calculated, %: C 62.91;
H 6.37; N 7.59; S 5.79. M 553.67.
Ethyl 2-amino-7,7-dimethyl-4-(4-methylphenyl)-
1-[4-(morpholin-4-ylsulfonyl)phenyl]-5-oxo-
1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (6i).
Pale yellow crystals, mp 189–191°C. IR spectrum, ν,
cm–1: 3442, 3360 (NH2), 3254 (sec. SO2N), 3041
(C–Harom), 2962 (C–Haliph), 1700 (C=O), 1643 (C=O),
Ethyl 2-amino-7,7-dimethyl-5-oxo-1-[4-(piperi-
din-1-ylsulfonyl)phenyl]-4-(pyridin-4-yl)-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (6f). Pale yellow
crystals, mp 158–159°C. IR spectrum, ν, cm–1: 3436,
3361 (NH2), 3254 (sec. SO2N), 3056 (C–Harom), 2950
(C–Haliph), 1690 (C=O), 1640 (C=O), 1308, 1153
1
1316, 1160 (SO2). H NMR spectrum, δ, ppm: 0.93 s
(6H, CH3), 1.12 t (3H, CH3), 1.80 s (2H, CH2), 1.96 t
(4H, CH2), 2.32 s (2H, CH2), 2.51 s (3H, CH3), 3.21 t
(4H, CH2), 4.10 q (2H, OCH2), 4.45 s (1H, CH),
4.71 br.s (2H, NH2, D2O-exchangeable), 6.47 d (2H,
CH), 6.83 d (2H, CH), 7.36 d (2H, CH), 7.51 d (2H,
CH). Mass spectrum (EI), m/z (Irel, %): 579.02 (7)
[M]+, 362.07 (100). Found, %: C 63.97; H 6.20;
N 7.00; S 5.28. C31H37N3O6S. Calculated, %: C 64.23;
H 6.43; N 7.25; S 5.53. M 579.71.
1
(SO2). H NMR spectrum, δ, ppm: 0.93 s (6H, CH3),
1.05 t (3H, CH3), 1.13–1.18 m (6H, CH2), 1.35 s (4H,
CH2), 2.40 t (4H, CH2), 4.21 q (2H, OCH2), 4.36 s
(1H, CH), 6.64 d (2H, CH), 6.91 d (2H, CH), 7.05 br.s
(2H, NH2, D2O-exchangeable), 7.30 d (2H, CH),
7.53 d (2H, CH). Mass spectrum (EI), m/z (Irel, %):
563.88 (10) [M]+, 205.70 (100). Found, %: C 63.57;
H 6.22; N 9.80; S 5.48. C30H36N4O5S. Calculated, %:
C 63.81; H 6.43; N 9.92; S 5.68. M 564.70.
Ethyl 2-amino-4-(4-methoxyphenyl)-7,7-dimeth-
yl-1-[4-(morpholin-4-ylsulfonyl)phenyl]-5-oxo-
1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (6j).
Pale yellow crystals, mp 198–200°C. IR spectrum, ν,
cm–1: 3442, 3362 (NH2), 3251 (sec. SO2N), 3070
(C–Harom), 2920 (C–Haliph), 1700 (C=O), 1644 (C=O),
Ethyl 2-amino-7,7-dimethyl-1-[4-(morpholin-4-
ylsulfonyl)phenyl]-5-oxo-4-phenyl-1,4,5,6,7,8-hexa-
hydroquinoline-3-carboxylate (6g). Pale yellow
needles, mp 192–193°C. IR spectrum, ν, cm–1: 3442,
3360 (NH2), 3255 (sec. SO2N), 3043 (C–Harom), 2950
(C–Haliph), 1670 (C=O), 1643 (C=O), 1315, 1152
1
1316, 1153 (SO2). H NMR spectrum, δ, ppm: 0.93 s
(6H, CH3), 1.08 t (3H, CH3), 1.86 s (2H, CH2), 1.96 t
(4H, CH2), 2.24 s (2H, CH2), 3.33 t (4H, CH2), 4.02 s
(3H, OCH3), 4.16 q (2H, OCH2), 4.25 s (1H, CH),
1
(SO2). H NMR spectrum, δ, ppm: 0.92 s (6H, CH3),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

AMMONIUM CHLORIDE-CATALYZED FOUR-COMPONENT SONOCHEMICAL SYNTHESIS
63
11. Shams, H.Z., Mohareb, R.M., Helal, M.H., and
4.56 br.s (2H, NH2, D2O-exchangeable), 6.87 d (2H,
CH), 7.22 d (2H, CH), 7.39 d (2H, CH), 7.42 d (2H,
CH). Mass spectrum (EI), m/z (Irel, %): 594.92 (9)
[M]+, 361.89 (100). Found, %: C 62.21; H 6.00;
N 6.80; S 5.12. C31H37N3O7S. Calculated, %: C 62.50;
H 6.26; N 7.05; S 5.38. M 595.71.
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15. Supuran, C.T. and Scozzafava, A., Expert Opin. Ther.
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Ethyl 2-amino-4-(furan-2-yl)-7,7-dimethyl-
1-[4-(morpholin-4-ylsulfonyl)phenyl]-5-oxo-
1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (6k).
Pale yellow crystals, mp 180–181°C. IR spectrum, ν,
cm–1: 3442, 3360 (NH2), 3250 (sec. SO2N), 3078
(C–Harom), 2950 (C–Haliph), 1700 (C=O), 1644 (C=O),
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19. Mader, M.M., Shih, C., Considine, E., Dios, A.D.,
Grossman, C.S., Hipskind, P.A., Lin, H.S., Lobb, K.L.,
Lopez, B., Lopez, J.E., Cabrejas, L.M., Richett, M.E.,
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1
1316, 1150 (SO2). H NMR spectrum, δ, ppm: 1.02 s
(6H, CH3), 1.35 t (3H, CH3), 1.41 s (2H, CH2), 1.85 s
(2H, CH2), 2.93 t (4H, CH2), 3.71 t (4H, CH2), 4.00 s
(1H, CH), 4.15 br.s (2H, NH2, D2O-exchaneable),
4.35 q (2H, OCH2), 6.68 d (2H, CH), 7.40 t (1H, CH),
7.50 d (2H, CH), 7.73 d (1H, CH), 7.99 d (1H, CH).
13C NMR spectrum, δC, ppm: 12.93 (CH3), 24.23 (2C,
CH3), 25.63 (2C, CH2), 34.42, 39.12, 45.11 (C4), 46.73
(CH2), 48.36 (2C, CH2), 56.23 (CH2), 111.60 (CH),
113.85 (CH), 127.30 (2C, CH), 129.91 (CH), 130.08
(2C, CH), 143.70 (2C), 152.06 (2C), 157.00, 160.85,
168.81 (C=O), 195.64 (C=O). Mass spectrum (EI), m/z
(Irel, %): 554.97 (18) [M]+, 361.09 (100). Found, %:
C 60.28; H 6.25; N 7.35; S 5.77. C28H33N3O7S. Cal-
culated, %: C 60.52; H 5.99; N 7.56; S 5.77. M 555.64.
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