An Efficient One-Pot Three-Component Synthesis of Some New Polyhydroquinolines via Enaminone Intermediates

Article abstract of DOI:10.1002/jhet.2886

For a wide spectrum of pharmacological effects of polyhydroquinolines, this study introduces a developed safe, simple, higher yields and fast method for the synthesis of some new hexahydroquinoline derivatives using one-pot three-component cyclocondensation reaction, via the reaction of 1,3-cyclohexanedione with primary amine and arylidinemalononitrile or salicylaldehyde derivatives. The prepared compounds were reacted with different reagents as N,N-dimethylformamide dimethylacetal, acetic anhydride, sulphuric acid, and hydrazine hydrate forming several polycyclic hexahydroquinoline and acridine derivatives. All these new compounds have been characterized by spectral data and expected to be effective pharmaceutical drugs.

Full text of DOI:10.1002/jhet.2886

Month 2017
An Efficient One-Pot Three-Component Synthesis of Some New
Polyhydroquinolines via Enaminone Intermediates
*
Omyma A. Abd Allah, and Asmaa H.A. Tamam
Antar A. Abdelhamid,
Chemistry Department, Faculty of Science, Sohag University, Sohag, Egypt
*
E-mail: omymatif66@yahoo.com
Additional Supporting Information may be found in the online version of this article.
Received November 29, 2016
DOI 10.1002/jhet.2886
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
For a wide spectrum of pharmacological effects of polyhydroquinolines, this study introduces a developed
safe, simple, higher yields and fast method for the synthesis of some new hexahydroquinoline derivatives
using one-pot three-component cyclocondensation reaction, via the reaction of 1,3-cyclohexanedione with
primary amine and arylidinemalononitrile or salicylaldehyde derivatives. The prepared compounds were
reacted with different reagents as N,N-dimethylformamide dimethylacetal, acetic anhydride, sulphuric acid,
and hydrazine hydrate forming several polycyclic hexahydroquinoline and acridine derivatives. All these
new compounds have been characterized by spectral data and expected to be effective pharmaceutical drugs.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
[11]. Different 1,2,3,4-tetrahydroquinolines have been
tested as potential drugs, for example, schistosomicide,
nicainoprol [12], and oxamniquine [13] are antiarrhythmic
drug, and virantmycin [14] is an antibiotic drug.
Tetrahydroquinoline L-689,560 is one of the most useful
NMDA antagonists yet found [15,16] (Fig. 1). In
continuation to our previous work [17], this study has been
undertaken to synthesize some new hexahydroquinolines
via one-pot three-component cyclocondensation reaction of
1,3-cyclohexanedione, aryledenmalononitrile, and amine as
reagents in aqueous medium expected to have an effective
pharmaceutical activities (Scheme 1), the higher effective
of the quinolone and acridine encouraged to synthesis of
16 new compounds of these nuclei.
Quinoline and some of its derivatives are the most
widespread N-heterocyclic compounds associated into
the structures of most pharmaceutical and antimicrobial
drugs [1]. Recently, much interest has been dedicated to the
synthesis of polyhydroquinoline compounds because of
their diverse therapeutic and pharmacological properties.
Various quinoline derivatives characterize moderate
toxicity and central nervous system stimulants [2,3]. Some
fluoroquinolines, for example, 8-difluoro-methoxy-1-ethyl-6-
fluoro-1,4-dihydro-7-[4-(2-methoxyphenyl)-1-pipernzinyl]-4-
oxoquinoline-3-carboxylic acid] and 7-(3,4-dihydro-4-phe
nyl-piperidnyl)-1,4-dihydro-6-fluoro-1-methyl-8-trifluorome
thyl-4-oxo-quinolone-3-carboxylic acid have been reported
as inhibitors for human immunodeficiency virus-1
replication through interference with the transcription
process [4–6]. The known quinoline nucleus existed in
different natural compounds like quinones, chloroquine,
and papaverine [7,8]. The two former nuclei are
antimalarial natural products, whereas the third one is a
smooth muscle relaxant, a coronary vasodilator, an
antispasmodic drug, and also primarily used in the
treatment of visceral spasm and vasospasm (especially
those involving the heart and the brain) [9,10].
Additionally, naturally occurring quinolone derivatives as
2-methyl-1,2,3,4-tetra-hydroquinoline exist in human brain.
Dynemycin is acting as antitumor and antibiotic effectives
RESULTS AND DISCUSSION
Firstly, the protocol for the previously mentioned
reaction has been established without any catalyst in
refluxing aqueous condition, the desired product not
prepared. The same reaction was employed incorporating
a small amount of triethylamine as catalytic amount
under the same reflux condition, so an excellent yield
(about 80%) of the desired hexahydroquinolines has been
obtained. The target compounds 2-amino-3-cyano-
hexahydroquinoline derivatives 2a–e were prepared in a
very good yield, via
a
one-pot three-component
© 2017 Wiley Periodicals, Inc.

A. A. Abdelhamid, O. A. Abd Allah, and A. H. A. Tamam
Vol 000
the amines under aqueous conditions. The formed
enaminone contains a nucleophilic character of both of
enamine and enone [19]. Step 2 comprises Michael addition
reaction with intramolecular cyclization between enaminone
and different arylidenemalononitriles affording the final
product hexahydroquinoline derivatives 2a–e (Scheme 2).
Moreover, under the same previous condition, two molar
ratio 1,3-cyclohexandione 1 was reacted with equimolar
ratio of the aldehyde, namely, salicylaldehyde or p-bro
mosalicylaldehyde and ethyl glycinate hydrochloride in
presence of two molar ratio of triethylamine in refluxing
ethanol to afford ethyl-2-[9-(2-hydroxyphenyl)-1,8-dioxo-
Figure 1. The oxamniquine, nicainoprol, virantmycin, and
tetrahydroquinoline L-689,560.
1,2,3,4,5,6,7,8,9,10-decahydroacridin-10-yl]acetate
and
ethyl-2-[9-(3-bromo-2-hydroxyphenyl)-1,8-dioxo-1,2,3,4,5,6,
7,8,9,10-deca-hydroacridin-10-yl]-acetate [20] 3a,b,
respectively, in good yields 80% (Scheme 1). In our previous
work, compound 3b was obtained with another synthetic
route [20] that leads to relatively lower yield. The structures
Scheme 1. Synthesis of hexahydroquinoline 3a,b and octahydroacridine
derivatives 2e–f.
1
of these compounds were established using IR, H-NMR,
13C-NMR, and MS spectral analyses.
When an equimolar ratio of compound 2b was subjected
to react with N,N-dimethylformamide dimethylacetal in
boiling dimethylformamide (DMF) resulting in the
formation of [9-(2-hydroxyphenyl)-N0-[3-cyano-1-(4-meth
ylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-2-yl]-N,N-
dimethylimidoformamide (4). 1H-NMR spectrum (DMSO-
d6) revealed a singlet signal at δ 7.67 due to the olefinic
proton CH═N and two singlet signals due to the
dimethylamino group at δ 2.90 and 2.34 ppm (cf.
experimental).
cyclocondensation reaction of 1,3-cyclohexanedione 1
with p-toluidine and
a
series of substituted
However, the reaction of the target compound 2b
with refluxing acetic anhydride leads to the formation
of pyrimidohexahydroquinoline derivative 5 in 68%
yield. During an attempt to recrystallize compound 5
arylidinemalononitrile (benzylidinemalononitrile, p-chloro
benzylidinemalononitrile [17], and p-methoxybenzylidine
malono-nitrile) forming 2a–c derivatives, in addition to
the reaction of 1,3-cyclohexanedione 1 with diamens
examply (1,2-diaminoethane or 1,4-diaminobenzene) and
p-chlorobenzylidinemalono-nitrile in refluxing ethanol
containing a catalytic amount of triethylamine. The
condensation reaction of 1,2-diaminoethane took place via
the two amino groups but of 1,4-di-aminobenzene took
place via one amino group only forming ethane-1,2-bis-[2-
amino-1-(4-methylphenyl)-5-oxo-4-(4-chlorophenyl)(1,4,5,6,
7,8-hexahydroquinolone-3-carbonitrile] and 2-amino-4-(4-
chloro phenyl)-1-(4-aminophenyl)-5-oxo-1,4,5,6,7,8-hexahy
droquinoline-3-carbonitrile derivatives 2d,e, respectively
(Scheme 1). The spectral analyses of compound 2e pointed
to the presence of an ethanol molecule joined with
octahydroacridine moiety during the crystal lattice building.
The molecular structures of the products 2a–e were
from DMF,
a
DMF molecule was joined with
pyrimidohexahydroquinoline moiety during the crystal
lattice building. The presence of the DMF molecule was
1
proven in the basis of H-NMR and 13C-NMR spectral
analyses. 1H-NMR (DMSO-d6) spectrum pointed to a
Scheme 2. The reaction mechanism of formation of a hexahydroquinoline
derivatives (2a–e).
1
illustrated from their IR, H-NMR, and 13C-NMR spectral
analyses. The empirical mechanism for this transformation
can be rationalized through two different steps [18]. Step 1
involves the formation of the required cyclohex-2-
enaminones from the reaction of 1,3-cyclohexanedione with
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Synthesis of Some Quinoline Derivatives
singlet signal at δ 7.97 due to CH group and two singlet
signals at δ 2.90 and 2.75 due to two CH3 groups of
DMF molecule. Also, 13C-NMR (DMSO-d6) spectrum
showed three signals of C═O carbon at 196.09 of DMF,
in addition to another two carbonyl carbons at 172.70
and 162.13 ppm of pyrimidohexahydroquinoline moiety
and two CH3 carbons at 21.45 and 21.27 of DMF in
addition to another CH3 carbon at 28.36 ppm of
pyrimidohexahydroquinoline moiety. The reaction of
compound 2b with concd sulphuric acid took place at
25°C via the acid hydrolysis of the cyano group and the
oxidation reaction of the amino group to form the keto
carboxylic acid derivative 6. The structural elucidation of
the synthesized compounds 5 and 6 was carried out by
ester derivative 7. The structure of this compound has
been further confirmed by refluxing the parent compound
2-amino-3-cyano-hexahydroquinoline derivative 2b with
sulphuric acid in absolute ethanol for 4 h. The spectral
data of the product were typical with those of compound
7 (Scheme 3). The condensation reaction of compound 7
with equimolar amounts of phenyl hydrazine and
catalytic amount of trifloroacetic acid was studied. This
reaction took place only at the carbonyl group of
cyclohexenone moiety resulting in phenylhydrazone
derivative 8 in a good yield (Scheme 3). The structures of
these new products 7 and 8 have been unambiguously
confirmed by IR, 1H-NMR, and 13C-NMR spectral
analyses.
Basic hydrolysis of compound 3b affording the
corresponding carboxylic acid derivative [9-(3-bromo-2-
hydroxyphenyl)-2, 3, 4, 5, 6, 7, 8, 9-octahydroacridin-
10(1H)-yl] acetic acid (9), during its recrystallization from
ethanol, an ethanol molecule was joined with
octahydroacridine moiety during the crystal lattice
building. IR, 1H-NMR, and 13C-NMR analyses gave a
good evidence for its structure. The hydrazide derivatives
1
IR, H-NMR, and 13C-NMR spectral analyses, where IR
spectrum of compound 6 revealed the existence of the
three strong stretching vibrations at ν 1705, 1671, and
1631 cmꢀ1 due to three carbonyl groups functions of 2,5-
dioxo-octahydroquinoline-3-carboxylic acid. The keto
acid derivative 6 was allowed to react with absolute
ethanol in the presence of concd sulphuric acid under
reflux for 4 h to form the expected corresponding ethyl
Scheme 3. The reaction take place on 2-amino-4-(4-chlorophenyl)-1-(4-methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (2b).
Journal of Heterocyclic Chemistry
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A. A. Abdelhamid, O. A. Abd Allah, and A. H. A. Tamam
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Scheme 4. The reaction take place on ethyl-2-[9-(3-subsituted-2-
hydroxyphenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10-decahydro-acridin-10-yl]
acetate (3a,b).
chromatography, and all melting points are uncorrected
and were recorded on Melt-Tem II melting point apparatus.
Synthesis of 2-amino-1-(4-methylphenyl)-5-oxo-4-(aryl)-
1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (2a–c) (general
procedure).
To a solution of 1,3-cyclohexanedione
(3.36 g, 0.03 mol) and p-toludine (3.21 g, 0.03 mol) in
ethanol (40 mL), a catalytic amount of triethylamine was
added. The reaction mixture was heated under reflux for
3 h. Arylidinemalononitrile, namely, benzylidenemalono
trile, 4-chlorobenzylidenemalononitrile, and 4-methoxy
benzylidenemalononitrile (0.03 mol) was added to the
reaction mixture while reflux for another 3 h. The
separated solid was filtered on hot washed with ethanol
and crystallized from the suitable solvent.
2-Amino-4-phenyl-1-(4-methylphenyl)-5-oxo-1,4,5,6,7,8-he
xahydroquinoline-3-carbonitrile (2a).
Crystalized as
brown crystal from ethanol; yield 70%; mp 290–292°C;
IR (λmax, cmꢀ1): 3470 m, 3312 m (NH2), 3062–3030 w
(CHarom.), 2946–2888 m (CHaliph.), 2178 m (C☰N), 1632
s
(C═O), 1610 s
(C═C); 1H-NMR (400 MHz,
10a,b were prepared via the reaction of the acridine
derivatives 3a,b with hydrazine hydrate in boiling
ethanol. When compound 10a was reacted with p-
DMSO-d6), δppm: 7.31–7.16 (m, 9H, CHarom.), 5.26 (s,
2H, NH2, disappeared by D2O), 4.51 (s, 1H, CH–Ar),
2.40 (s, 3H, CH3–Ar), 2.29–2.19 (t, 2H, CH2–C═O),
1.94–1.81 (t, 2H, CH2–C═C), 1.66–1.61 (m, 2H, CH2–
CH2–CH2); 13C-NMR (100 MHz, DMSO-d6), δppm:
195.47 (C═O), 152.91, 151.59, 147.08, 139.84, 134.11
(5–C), 131.04, 130.02, 128.82, 127.19, 126.66 (9–CH),
121.88 (C), 113.18 (C☰N), 61.03 (C), 56.53 (CH2–
C═O), 36.53 (CH), 28.20, 21.19 (2–CH2), 21.10 (CH3);
analysis: calculated for C23H21N3O (355.43): C, 77.71;
H, 5.96; N, 11.82%. Found: C, 77.65; H, 5.81; N, 11.97%.
chlorobenzaldehyde in DMF via
a
nucleophilic
condensation reaction, [9-(2-hydroxyphenyl)]-N0-[(1E)-
ethylidene]-2-[2,3,4,5, 6, 7,8,9-octahydroacridin-10(1H)-
yl]acetohydrazide (11) has been formed in 50% yield
(Scheme 4). All the new compounds were investigated
with spectral analyses as shown in the experimental section.
CONCLUSION
2-Amino-4-(4-chlorophenyl)-1-(4-methylphenyl)-5-oxo-1,4,
Regarding to the importance of the polyhydroquinolines
effects, a developed safe method for the synthesis of
some new hexahydroquinoline derivatives using one-pot
three-component cyclocondensation reaction, via the
combination of 1,3-cyclohexanedione with primary
amine and arylidinemalononitrile or the combination
of 1,3-cyclohexanedione with primary amine and
salicylaldehyde derivatives was carried out.
5,6,7,8-hexahydroquinoline-3-carbonitrile (2b). Crystalized as
pale yellow crystal from DMF; yield: 79%; mp 300°C; IR
(λmax, cmꢀ1): 3472 s, 3325 s (NH2), 3032 w (CHarom.),
2972–2879 w (CHaliph.), 2177 m (C☰N), 1631 s (C═O);
1H-NMR (400 MHz, DMSO-d6), δppm: 7.39–7.29 (m,
8H, CHarom.), 5.32 (s, 2H, NH2, disappeared by D2O),
4.51 (s, 1H, CH–Ar), 2.4 (s, 3H, CH3), 2.23–2.19
(t, J = 8 Hz, 2H, CH2–C═O), 1.93–1.81 (t, 2H, CH2–
C═C), 1.65–1.61 (m, 2H, CH2–CH2–CH2); 13C-NMR
(100 MHz, DMSO-d6), δ ppm: 195.45 (C═O), 153.14,
151.70, 146.07, 139.86, 133.96, 131.26 (6–C), 131.03,
130.10, 129.13, 128.79 (8–CH), 121.78 (C), 112.72
(C☰N), 60.26 (C), 36.45 (CH), 36.21, 28.23, 21.22 (3–
CH2), 21.06 (CH3); analysis: calculated for C23H20N3OCl
(389.87): C, 70.85; H, 5.18; N, 10.78%. Found: C, 70.76;
H, 5.27; N, 10.71%.
EXPERIMENTAL
All chemical reagents and instruments were bought from
Aldrich, Merck, and used directly without further
purification. Our products were investigated by IR spectra
measured on a Nicolet 710 Fourier transform infrared
spectroscopy spectrometer. 1H-NMR and 13C-NMR
spectra were recorded in deuterated dimethyl sulfoxide at
400 and 100 MHz on a BRUKER spectrometer and
DELTA 2-NMR spectrometer using tetramethylsilane as
an internal reference. The purity of the substances and the
progress of the reactions were screened on thin-layer
2-Amino-4-(4-methoxyphenyl)-1-(4-methylphenyl)-5-oxo-1,
4,5,6,7,8-hexahydroquinoline-3-carbonitrile (2c). Crystalized
as brown crystal ethanol; yield 72%; mp 252°C; IR (λmax
,
cmꢀ1): 3468 m, 3318 m (NH2), 3039 w (CHarom.), 2941–
1
2838 w (CHaliph.), 2180 m (C☰N), 1634 s (C═O); H-
NMR (400 MHz, DMSO-d6), δppm: 7.38–6.88 (m, 8H,
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Month 2017
Synthesis of Some Quinoline Derivatives
CHarom.), 5.12 (s, 2H, NH2, disappeared by D2O), 4.48 (s,
1H, CH–Ar), 3.75 (s, 3H, –O–CH3), 2.41 (s, 3H, CH3–Ar),
2.21–2.19 (t, J = 4 Hz, 2H, –CH2–C═O), 1.94–1.81 (t, 2H,
CH2–C═C), 1.66–1.61 (m, 2H, CH2–CH2–CH2); 13C-NMR
(100 MHz, DMSO-d6), δ ppm: 195.36 (C═O), 158.39,
152.43, 151.47, 139.81, 139.41, 134.25 (6–C), 131.02,
130.02,128.23, 114.37 (8–CH), 121.82 (C), 113.67 (C☰N),
61.59 (C), 55.59 (O–CH3), 36.59 (CH2–C═O), 35.72 (CH),
28.17, 21.21 (2–CH2), 21.15 (CH3); analysis: calculated for
C24H23N3O2 (385.45): C, 74.78; H, 6.02; N, 10.90%.
Found: C, 74.69; H, 6.15; N, 10.83%.
lattice); 13C-NMR (100 MHz, DMSO-d6), δppm: 195.35
(C═O), 154.04, 152.24, 150.27, 146.25, 131.19 (5–C),
130.52, 129.08, 128.72, 114.82 (8–CH), 123.69, 121.85 (2–
C),112.51 (C☰N), 59.83, 56.52 (2–C), 36.49 (CH), 36.16,
28.15, 21.12, 18.97 (3–CH2); analysis: calculated for
C22H19N4OCl (390.86): C, 67.59; H, 4.90; N, 14.33%.
Found: C, 67.43; H, 4.86; N, 14.37%.
Synthesis of ethyl-2-[9-(2-hydroxyphenyl)-1,8-dioxo-1,2,3,4,5,
6,7,8,9,10-decahydroacridin-10-yl]acetate and ethyl-2-[9-(3-bro
mo-2-hydroxyphenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10-de cahydroac
ridin-10-yl]acetate (3a,b) (general procedure). To a mixture
of 1,3-cyclohexanedione (3.36 g, 0.03 mol), ethyl glycinate
hydrochloride (2.09 g, 0.015 mol), and the appropriate
aldehyde; salicaldehyde (1.58 mL, 0.015 mol) or 5-bromo-
2-hydroxy benzaldehyde (3.015 g, 0.015 mol) in ethanol
(30 mL), triethylamine (2.09 g, 0.015 mol) was added. The
reaction mixture was heated under reflux for 5 h at 80–85°C
left to cool, and the separated solid was filtered off, dried,
and recrystallized from ethanol.
Synthesis of ethane-1,10-1,2-diyl-bis-[2-amino-5-oxo-4-(4-
chlorophenyl)-1,4,5,6,7,8–hexahydroquinolone-3-carbonitrile]
and 2-amino-1-(4-aminophenyl)-4-(4-chlorophenyl)-5-oxo-1,4,
5,6,7,8-hexahydroquinoline-3-carbonitrile (2d,e).
To a
solution of 1,3-cyclohexanedione (0.896 g, 0.008 mol) and
1,2-diaminoethane or 1,4-diaminobenzene (0.004 mol) in
ethanol (20 mL), a catalytic amount of triethylamine was
added, and the reaction mixture was heated under reflux
for 3 h. 4-Chlorobenzylidene- malononitrile (1.52 g,
0.008 mol) was added to the reaction mixture while reflux
9-(2-hydroxyphenyl)-1,8-dioxo-2,3,4,5,6,7,8,9-octahydroacridi
ne-10(1H)-yl)ethylacetate (3a).
Yellow crystal from
methanol; yield 77%; mp 230–232°C; IR (λmax, cmꢀ1):
3111 br (OH), 3061 w (CHarom.), 2981–2870 w (CHaliph.),
1739 vs (C═Oester), 1648 s, 1630 s (2C═Ocyclic), 1593 s
for additionally
5
h. The reaction mixture was
concentrated and cooled; the formed precipitate was
filtered off and crystallized from the proper solvent.
1
(C═C); H-NMR (400 MHz, DMSO-d6), δ ppm: 9.58 (s,
Ethane-1,10-1,2-diyl-bis-[2-amino-1-(4-methylphenyl)-5-oxo-4-
(4-chlorophenyl)(1,4,5,6,7,8-hexahydroquinolone-3-carbonitrile]
(2d). Brown crystal from ethanol; yield 73%; mp 210–212°
1H, OH, disappeared by D2O), 6.99–6.66 (m, 4H, CHarom.),
4.99 (s, 1H, CH–Ar), 4.83 (s, 2H, N–CH2–C═O), 4.28–
4.22 (q, J = 8 Hz, 2H, O–CH2–CH3), 2.90–2.86, 2.44–2.40
(t, J = 8 Hz, 4H, 2CH2–CH2–C═O), 2.29–2.27 (t, J = 8 Hz,
4H, 2CH2–C═C), 1.99–1.94, 1.82–1.79 (m, 4H, 2CH2–
CH2–CH2), 1.28–1.25 (t, J = 8 Hz, 3H, –CH2–CH3); 13C-
NMR (100 MHz, DMSO-d6), δ ppm: 198.00 (2–C═Ocyclic),
169.68 (C═Oester), 156.03 (2–C), 153.47, 132.76 (2–C),
128.51, 127.93, 120.49, 117.22 (4–CH), 114.95 (2–C),
62.18 (CH2–CH3), 47.75 (CH2–N), 35.98 (CH), 26.07,
25.71, 20.95 (6–CH2), 14.40 (CH3); MS (m/z, ɪ%): 395
(95.82) (M+), 377 (52.37), 339 (25.86), 308 (28.93), 302
(100.00), 290 (74.46), 274 (77.73), 262 (26.18), 199
(62.77); analysis: calculated for C23H25NO5 (395.44): C,
69.85; H, 6.38; N, 3.54%. Found: C, 69.91; H, 6.43; N,
3.47%.
C; IR (λmax, cmꢀ1): 3313 m, 3201 m (NH2), 3051 w
(CHarom.), 2950–2872 w (CHaliph.), 2176 m (C☰N), 1650 s
1
(C═O), 1613 s (C═C); H-NMR (400 MHz, DMSO-d6),
δppm: 7.33–7.18 (m, 8H, CHarom.), 6.13 (s, 4H, 2NH2,
disappeared by D2O), 4.44 (s, 2H, 2CH–Ar), 3.97–3.94 (t,
J = 8 Hz, 2H, N–CH2), 3.74–3.71 (t, J = 8 Hz, 2H, CH2–
N), 2.86–2.82, 2.56–2.51 (t, 4H, 2CH2CH2CH2–C═O),
2.27–2.24 (t, J = 4 Hz, 4H, 2CH2CH2CH2–C═O), 2.08–
1.89 (m, 4H, 2CH2CH2CH2–C═O);13C-NMR (100 MHz,
DMSO-d6), δ ppm: 195.43 (2–C═O), 153.48, 152.17,
145.19, 131.28 (8–C), 128.92, 128.79 (8–CH), 121.70 (2–
C), 114.60 (2–C☰N), 62.99 (2–C), 42.47 (2–CH2–N),
36.22 (2–CH), 35.95, 26.42, 21.29 (6–CH2); analysis:
calculated for C34H30N6O2Cl2 (625.54): C, 65.27; H, 4.84;
N, 13.43%. Found: C, 65.17; H, 4.76; N, 13.51%.
9(2-hydroxy-5-bromophenyl)-1,8-dioxo-2,3,4,5,6,7,8,9-octa
hydroacridine-10(1H)yl)ethyl acetate [18] (3b).
Yellow
2-Amino-1-(4-aminophenyl)-4-(4-chlorophenyl)-5-oxo-1,4,5,6,
7,8-hexahydroquinoline-3-carbonitrile (2e).
White crystal
crystal; yield 80%; mp 242°C; IR (λmax, cmꢀ1): 3150
(OH), 3049 w (CHarom.), 2980–2888 w (CHaliph.), 1737
vs (C═Oester), 1631 s (C═Ocyclic), 1593 s (C═C); 1H-
NMR (400 MHz, DMSO-d6), δ ppm: 9.84 (s, 1H, OH,
disappeared by D2O), 7.14–6.65 (m, 3H, CHarom.), 4.96
(s, 1H, CH–Ar), 4.85 (s, 2H, –N–CH2–C═O), 4.28–4.23
(q, J = 8 Hz, 2H, –CH2–CH3), 2.89–2.86, 2.46–2.42 (t,
J = 8 Hz, 4H, 2CH2–CH2–C═O), 2.31–2.28 (t, J = 8 Hz,
4H, 2CH2–C═C), 2.00–1.94, 1.84–1.77 (m, 4H, 2
CH2–CH2–CH2), 1.28–1.26 (t, J = 8 Hz, 3H, –CH2–
CH3); 13C-NMR (100 MHz, DMSO-d6), δ ppm: 197.60
from ethanol; yield 64%, mp 264°C.; IR (λmax, cmꢀ1): 3453
m, 3334 m (NH2), 3034 w (CHarom.), 2944–2819 w
(CHaliph.), 2172 m (C☰N), 1641 s (C═O), 1608 s (C═C);
1H-NMR (400 MHz, DMSO-d6), δppm: 7.37–6.67 (m, 8H,
CHarom.), 5.48, 5.19 (s, 4H, 2NH2, disappeared by D2O),
4.50 (s, 1H, CH–Ar), 4.21 (s, 1H,OH ethanol molecule in
the crystal lattice), 3.48–3.45 (q, 2H,CH2 ethanol molecule
in the crystal lattice), 2.23–2.18 (t, 2H, CH2–C═O), 2.04–
2.00 (t, J = 8 Hz, 2H, CH2–C═C), 1.86–1.62 (m, 2H, CH2–
CH2–CH2), 1.09 (t, 3H, CH3 ethanol molecule in the crystal
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. A. Abdelhamid, O. A. Abd Allah, and A. H. A. Tamam
Vol 000
(2–C═Ocyclic), 169.62 (C═Oester), 156.16 (2–C), 153.55,
135.48, 131.05 (3–C), 130.66, 119.58, 114.34 (3–CH),
111.63 (2–C), 62.02 (CH2–CH3), 47.77 (CH2–N), 36.02
(CH), 26.53, 26.12, 20.98 (6–CH2), 14.51 (CH3); MS
(m/z, ɪ%): 479 (0.56), 478 (0.86) (M+ + 2), 477 (4.68),
476 (25.75) (M+ + 1), 475 (90), 474 (30.26) (M+), 433
(1.44), 404 (4.46), 384 (0.9), 300 (1.59), 281 (1.02), 253
(1.56), 206 (4.95), 91 (5.9), 91.95 (3.4), 52 (0.91), 51
(1.42), 50 (0.62); analysis: calculated for C23H24NO5Br
(474.34): C, 58.23; H, 5.11; N, 2.95%. Found: C, 58.15;
H, 5.23; N, 2.83%.
28.41, 21.60 (3–CH2), 21.31, 21.18 (2–CH3); MS (m/z, ɪ
%): 433 (1.61) (M+ + 2), 431 (5.79) (M+), 336 (1.24), 320
(23.81), 279 (1.03), 91.05 (8.46), 65 (6.37); analysis:
calculated for C25H22N3O2Cl (431.91): C, 69.51; H, 5.14;
N, 9.73%. Found: C, 69.63; H, 5.07; N, 9.68%.
Synthesis of 4-(4-chlorophenyl)-1-(4-methylphenyl)-2,5-
dioxo-1,2,3,4,5,6,7,8-octahydro-quinolone-3-carboxylic acid
(6). A solution of compound 2b (2.0 g, 0.0051 mol) in
concd H2SO4 (20 mL) was stirred for 4 h at room
temperature, and the reaction mixture was poured into
ice-cold water. The formed precipitate was collected,
filtered of, washed with water, and recrystallized from
ethanol as pale yellow crystal, yield; 89%; mp 245°C;
IR (λmax, cmꢀ1): 3192 br (OHacid), 3034 w (CHarom.),
2948–2867 w (CHaliph.), 1705 s (C═Oacidic), 1671 s
(C═Oamidic), 1631 s (C═Ocyclic), 1601 s (C═C);1H-NMR
Synthesis of N0-[3-cyano-9-(4-chlorophenyl)-1-(4-methyl
phenyl)-5-oxo-1,4,5,6,7,8-hexa hydroquinolin-2-yl]-N,N-dimethy
limidoformamide (4). A solution of compound 4b (3.12 g,
0.008 mol) and DMF/DMA (1.1 mL, 0.008 mol) in DMF
(40 mL) was refluxed for 5 h, cooled, and then poured into
ice-cold water. The formed precipitate was collected by
filtration and recrystallized from ethanol as pale brown
crystal yield 93%; mp 228°C; IR (λmax, cmꢀ1): 3039 w
(CHarom.), 2970–2807 w (CHaliph.), 2182 m (C☰N), 1635 s
(C═Ocyclic ketone), 1610 s (C═N); 1H-NMR (400 MHz,
DMSO-d6), δppm: 7.67 (s, 1H, CH═N), 7.38–7.13 (m, 8H,
CHarom.), 4.62 (s, 1H, CH–Ar), 2.90 (s, 3H, CH3–N), 2.34
(s, 3H, CH3–N), 2.20 (s, 3H, CH3–Ph), 2.04–1.99 (t, 2H,
CH2CH2CH2–C═O), 1.83–1.80 (t, 2H, CH2CH2CH2–
C═O),1.67–1.63 (m, 2H, CH2CH2CH2–C═O); 13C-NMR
(100 MHz, DMSO-d6), δ ppm: 195.39 (C═O), 157.68,
155.64, 153.92, 145.69, 137.99, 136.37, 131.45, 130.11,
129.64, 129.34, 128.85, 122.06, 111.60 (C☰N), 70.71 (C),
39.96 (CH), 37.97, 36.55, 34.28 (3–CH2), 28.31 (CH3–Ar),
21.27, 21.13 (2–CH3–N); analysis: calculated for
C26H25N4OCl (444.95): C, 70.17; H, 5.67; N, 12.59%.
Found: C, 70.21; H; 5.61; N, 12.47%.
(400 MHz, DMSO-d6), δ ppm: 7.76 (s, 1H, OHacid
,
disappeared by D2O), 7.41–7.10 (m, 8H, CHarom.), 4.61
(d, J = 4 Hz, 1H, CH–COOH), 3.59 (d, J = 4 Hz,
1H, CH–Ar), 2.37 (s, 3H, CH3–Ph), 2.30–2.26
(t, J = 8 Hz, 2H, CH2CH2CH2–C═O), 2.10–2.05 (t, 2H,
CH2CH2CH2–C═O), 1.92–1.87 (m, 2H, CH2CH2CH2–
C═O); 13C-NMR (100 MHz, DMSO-d6), δ ppm: 195.51
(C═Ocyclic), 169.64 (C═Oacid), 167.62 (C═Oamidic),
156.78, 140.06, 138.53, 135.06, 132.00 (5–C), 130.26,
130.04, 129.31, 129.10 (8–CH), 114.82 (C), 56.04 (C),
37.88 (CH), 36.36, 28.08, 21.88 (3–CH2), 21.12 (CH3);
MS (m/z, ɪ%): 409 (0.27) (M+), 405 (0.76), 380 (0.61),
366 (9.14), 364 (29.15), 91 (16.91); analysis: calculated
for C23H20NO4Cl (409.86): C, 67.39; H, 4.92; N, 3.41%.
Found: C, 67.31; H, 4.80; N, 3.48%.
Synthesis of ethyl [4-(4-chlorophenyl)-1-(4-methylphenyl)-
2,5-dioxo-1,2,3,4,5,6,7,8-octa hydroquinoline]-3-carboxylate (7).
Method 1. To a solution of compound 2b (2.0 g, 5.13
mmol) in absolute ethanol (50 mL), concd H2SO4 (2 mL)
was added then allowed to heat under reflux for 4 h,
cooled, and poured into ice-cold water. The formed
precipitate was collected, filtered, and recrystallized from
ethanol as white crystal, yield 70%; mp 1600°C.
Synthesis of 2-methyl-9-(4-chlorophenyl)-10-(4-methylphenyl)-
5,8,9,10-tetrahydropyr-imido[4,5-b]quinoline-4,6(3H,7H)-dione
(5). A solution of compound 2b (0.78 g, 0.002 mol) in dry
acetic anhydride (20 mL) was refluxed for 3 h; the solvent
was evaporated under reduced pressure, and the formed
precipitate was collected and recrystallized from DMF as
off white crystal, yield 68%; mp >320°C; IR (λmax
,
Method 2.
To a solution of compound 6 (1.58 g,
cmꢀ1): 3395 m (NH), 3042 w (CHarom.), 2951–2859 w
(CHaliph.), 1682 s (C═Oamidic), 1641 s (C═Ocyclic ketone),
0.004 mol) in absolute ethanol (40 mL) was added concd
H2SO4 (1.5 mL). The reaction mixture was refluxed for 4 h,
cooled, and then poured into ice-cold water. The formed
precipitate was collected, filtered, and recrystallized from
1
1594 s (C═N); H-NMR (400 MHz, DMSO-d6), δ ppm:
12.06 (s, 1H, NH, disappeared by D2O),7.97 (s, 1H, CH
DMF molecule in the crystal lattice),7.37–7.17 (m, 8H,
CHarom.), 5.17 (s, 1H, CH–Ar), 2.9, 2.75 (s, 6H, 2CH3
DMF molecule in the crystal lattice), 2.40 (s, 3H, CH3–
Ph), 2.24–2.10 (m, 4H, CH2CH2CH2–C═O), 2.03 (s, 3H,
CH3–C═N), 1.87–1.68 (m, 4H, 2CH2);13C-NMR
(100 MHz, DMSO-d6), δ ppm: 195.29 (C═Ocyclic ketone),
162.74 (HC═ODMF molecule), 162.07 (C═Oamidic), 157.06,
154.57,153.66, 145.55, 138.14, 136.21, 131.00 (7–C),
130.17,130.05, 129.73, 128.39 (8–CH), 112.54, 101.18 (2–
C), 36.21, 31.27 (2–CH3DMF molecule), 36.68 (CH), 32.67,
ethanol as white crystal, yield 77%; mp 160°C; IR (λmax
,
cmꢀ1): 3252 m (NH), 3032 w (CHarom.), 2995–2868 w
(CHaliph.), 1739 vs (C═Oester), 1703 s (C═Oamidic), 1647 s
(C═Ocyclic), 1614
s
(C═C); 1H-NMR (400 MHz,
DMSO-d6), δppm: 7.40–7.07 (m, 8H, CHarom.), 4.68 (d,
J = 4 Hz, 1H, CH–COOEt), 4.25–4.22 (q, J = 4 Hz, 2H,
O–CH2–CH3), 3.92 (d, J = 4 Hz, 1H, CH–Ar), 2.37 (s, 3H,
CH3–Ph), 2.30 (t, 2H, CH2CH2CH2–C═O), 2.10–2.06 (t,
2H, CH2CH2CH2–C═O), 1.92–1.86 (m, 2H, CH2CH2CH2–
C═O), 1.25–1.22 (t, 3H, –CH2–CH3); 13C-NMR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis of Some Quinoline Derivatives
(100 MHz, DMSO-d6), δ ppm: 195.35 (C═Ocyclic), 168.02
(C═Oester), 165.91 (C═Oamidic), 156.56, 138.80, 138.47,
134.51, 132.30 (5–C), 130.43, 129.33, 129.28, 128.77 (8–
CH), 115.36 (C), 62.14 (CH2–CH3), 55.06, 37.04 (2–CH),
36.28, 27.96, 21.97 (3–CH2), 21.13 (CH3Ar), 14.46 (CH3–
CH2); analysis: calculated for C25H24NO4Cl (437.91): C,
68.56; H, 5.53; N, 3.19%. Found: C, 68.41; H, 5.65; N,
3.23%.
(t, 4H, 2CH2CH2CH2–C═O), 1.98, 1.84 (m, 4H,
2CH2CH2CH2–C═O), 1.08 (t, 3H,CH3 ethanol molecule
in the crystal lattice); 13C-NMR (100 MHz, DMSO-d6),
δ
ppm: 197.46 (2–C═Ocyclic), 170.98 (C═Oacid),
156.15,153.56, 135.66 (6–C), 131.19, 130.56, 119.50 (3–
CH), 114.40, 111.67 (4–C), 56.52 (CH2 ethanol
molecule), 47.83 (CH2–N), 36.08 (CH), 26.55, 26.22,
21.05 (6–CH2), 19.01 (CH3 ethanol molecule); analysis:
calculated for C21H20NO5Br (446.29): C, 56.51; H, 4.52;
N, 3.13%. Found: C, 56.38; H, 4.43; N, 3.27%.
Synthesis of ethyl[4-(4-chlorophenyl)-1-(4-methylphenyl)-
(5E)-2-oxo-5-(2-phenyl-hydrazinylidene)-1,2,3,4,5,6,7,8-octahydro
quinoline]-3-carboxylate (8). A mixture of compound 7
Synthesis of 2-[9-(2-hydroxyphenyl)-1,8-dioxo-1,2,3,4,5,
6,7,8,9,10 decahydroacridin-10-yl]acetohydrazide and 2-[9-
(3-bromo-2-hydroxyphenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10-decahy
dro-acridin-10-yl]acetohydrazide (10a,b) (general procedure).
A solution of compound 3a,b (0.005 mol) in hydrazine
hydrate (20 mL) was refluxed for 2 h, cooled, and then
triturated with ethanol. The precipitated solid obtained was
filtered off, dried, and recrystallized from DMF to furnish
compound 10a,b.
(0.65 g, 0.0015 mol), phenyl hydrazine (0.15 mL,
0.0015 mol), and catalytic amount of trifloroacetic acid in
ethanol (20 mL) was heated under reflux for 4 h. The
solvent was evaporated under reduced pressure, and the
formed precipitate was collected by filtration and
recrystallized from ethanol as green crystal, yield 76%;
mp 138–140°C; IR (λmax, cmꢀ1): 3252 m (NH), 3099–
3024 w (CHarom.), 2981–2836 w (CHaliph.), 1730 vs
(C═Oester), 1666 s (C═Oamidic), 1630 s (C═N), 1596 s
2-[9-(2-Hydroxyphenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10-deca
hydroacridin-10-yl]acetohyd-razide (10a). Yellow powder
1
(C═C); H-NMR (400 MHz, DMSO-d6), δppm: 8.97 (s,
1H, NH, disappeared by D2O), 7.44–6.68 (m, 13H,
CHarom.), 5.06 (d, J = 4 Hz, 1H, CH–COOEt), 4.25–4.20
(q, J = 4 Hz, 2H, O–CH2–CH3), 3.83 (d, J = 4 Hz, 1H,
CH–Ar), 2.36 (s, 3H, CH3–Ph), 2.62–2.58 (t, 2H,
CH2CH2CH2–C═O), 1.89–1.86 (t, 2H, CH2CH2CH2–
C═O), 2.12, 1.69 (m, 2H, CH2CH2CH2–C═O), 1.21–
1.19 (t, J = 4 Hz, 3H, –CH2–CH3); 13C-NMR (100 MHz,
from DMF; yield 90%; decomposed at 264°C; IR (λmax
,
cmꢀ1): 3362 br (OH), 3339 m, 3251 m (NH2, NH), 3051
w (CHarom.), 2926–2867 w (CHaliph.), 1668 s (C═Oamide),
1
1627 s (C═Ocyclic) 1582 s (C═C); H-NMR (400 MHz,
DMSO-d6), δppm: 11.05 (br, 1H, NH, disappeared by
D2O), 9.07 (s, 1H, OH, disappeared by D2O), 6.98–6.56
(m, 4H, CHarom.), 5.63 (broad, 2H, NH2, disappeared by
D2O), 5.20 (s, 1H, CH–Ar), 4.22 (s, 2H, –N–CH2–C═O),
2.51, 2.38–2.34 (t, 4H, 2CH2CH2CH2–C═O), 2.31–2.29,
2.07–2.01 (t, 4H, 2CH2CH2CH2–C═O), 1.82–1.78,
1.63–1.60 (m, 4H, 2CH2CH2CH2–C═O); 13C-NMR
(100 MHz, DMSO-d6), δ ppm: 195.74 (2–C═Ocyclic),
169.35 (C═Oamidic), 154.85, 148.49, 140.22, 134.62
(4–C), 128.55, 126.72, 119.29, 116.95 (4–CH), 110.92
(2–C), 46.77 (CH2–N), 27.93 (CH), 25.23, 22.47, 20.82
(6–CH2); MS (m/z, ɪ%): 381 (0.18) (M+), 269 (0.96), 199
(1.07), 180 (2.13), 167 (1.06), 94 (100.00), 66 (33.85);
analysis: calculated for C21H23N3O4 (381.42): C, 66.12;
H, 6.09; N, 11.01%. Found: C, 66.02; H, 6.23; N, 11.18%.
DMSO-d6),
δ
ppm:168.67
(C═Oester),165.27
(C═Oamidic),146.60, 142.01, 139.56, 139.45, 137.94,
135.15, 131.93, 115.87 (8–C), 130.14, 129.96, 129.53,
129.21, 128.68, 118.91, 112.86 (13–CH), 61.72 (CH2–
CH3), 55.56, 38.54 (2–CH), 26.78, 23.35, 21.30 (3–CH2),
21.12 (CH3Ar), 14.52 (CH3–CH2); analysis: calculated
for C31H30N3O3Cl (528.04): C, 70.50; H, 5.73; N,
7.95%. Found: C, 70.46; H, 5.78; N, 7.89%.
Synthesis of [9-(3-bromophenyl)-2,3,4,5,6,7,8,9-octahydro
acridin-10(1H)-yl]acetic acid (9).
To a solution of
compound 3b (2.37gm, 0.005 mol) in ethanol (40 mL)
was added NaOH solution (0.4gm, 0.01 mol in 5 mL
water). The reaction mixture was heated under reflux for
5 h, cooled, poured to cold water, and acidified with
concd HCl. The separated solid was filtered off, dried,
and recrystallized from ethanol, yield 97%; mp 237–239°
2-[9-(3-Bromo-2-hydroxyphenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,
9,10decahydroacridin-10-yl] acetohydrazide (10b). Yellow
powder from DMF; yield 92%; decomposed at 254°C; IR
(λmax, cmꢀ1): 3534 br (OH), 3333 m, 3209 m (NH2,
NH), 3087–3046 w (CHarom.), 2951–2870 w (CHaliph.),
1679 s (C═Oamide), 1637 s (C═Ocyclic), 1617 s (C═C);
1H-NMR (400 MHz, DMSO-d6), δppm: 11.65 (br, 1H,
NH, disappeared by D2O), 9.13 (s, 1H, OH, disappeared
by D2O), 7.01–6.50 (m, 3H, CHarom.), 5.65 (br, 2H,
NH2, disappeared by D2O), 5.14 (s, 1H, CH–Ar), 4.25
(s, 2H, N–CH2–C═O), 2.58–2.54, 2.40–2.36 (t, 4H,
2CH2CH2CH2–C═O), 2.29–2.21, 2.07–2.02 (t, 4H,
2CH2CH2CH2–C═O), 1.82–1.79, 1.62–1.60 (m, 4H,
2CH2CH2CH2–C═O); 13C-NMR (100 MHz, DMSO-d6),
C; IR (λmax
,
cmꢀ1): 3444 br (OHacid), 3110 br
(OHphenolic), 3015 w (CHarom.), 2972–2882 w (CHaliph.),
1
1707 s (C═Oacid), 1625 s (C═Ocyclic), 1585 s (C═C); H-
NMR (400 MHz, DMSO-d6), δ ppm: 13.29 (br, 1H,
OHacidic, disappeared by D2O), 9.77 (s, 1H, OHphenolic
,
disappeared by D2O), 7.10–6.67 (m, 3H, CHarom.), 4.98
(s, 1H, CH–Ar), 4.71 (s, 1H, N–CH2–C═O), 4.47 (q, 2H,
CH2 ethanol molecule in the crystal lattice), 3.2 (s, 1H,
OH disappeared by D2O,ethanol molecule in the crystal
lattice), 2.9, 2.5 (t, 4H, 2CH2CH2CH2–C═O), 2.30
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. A. Abdelhamid, O. A. Abd Allah, and A. H. A. Tamam
Vol 000
REFERENCES AND NOTES
δ ppm: 194.86 (2–C═Ocyclic) 168.97 (C═Oamide), 154.49,
149.10, 140.86, 137.41 (4–C), 130.96, 130.03, 129.55
(3–CH), 119.26, 110.58 (2–C), 46.72 (CH2–N), 28.56
(CH), 25.33, 22.52, 20.82 (6–CH2); analysis: calculated
for C21H22N3O4Br (460.32): C, 54.79; H, 4.82; N,
9.13%. Found: C, 54.64; H, 4.75; N, 9.27%.
Synthesis of 1-{N0-(4-chlorobenzylidine)[9-(2-hydroxyphe
nyl)-1,8-dioxo-2,3,4,5,6,7,8,9-octahydroacridin-10(1H)-yl]}ace
tohydrazide (11). A mixture of compound 10a (0.38 g,
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0.001 mol), p-chlorobenzaldehyde (0.14 g, 0.001 mol),
and DMF (4 mL) in dioxane (20 mL) were heated under
reflux for 5 h. The solvent was evaporated under reduced
pressure, and the formed precipitate was filtered off and
recrystallized from ethanol as brown crystal in yield 50%;
mp 288–290°C; IR (λmax, cmꢀ1): 3351 br (OH), 3283 m
(NH), 3050 w (CHarom.), 2932–2864 w (CHaliph.), 1622 s
(C═Oamide) and (C═Ocyclic), 1561 s (C═N); 1H-NMR
(400 MHz, DMSO-d6), δppm: 10.47 (s, 1H, OH,
disappeared by D2O), 8.47 (s, 1H, N═CH–Ph), 7.87–
7.85, 7.53–7.51 (d, 4H, CHarom.), 6.97–6.65 (m, 4H,
CHarom.), 5.34 (s, 2H, N–CH2–C═O), 5.29 (s, 1H, CH–
Ar), 4.3 (q, 2H, CH2, an ethanol molecule in the crystal
lattice), 3.46 (s, 1H, NH, disappeared by D2O), 3.2 (s,
1H, OH an ethanol molecule in the crystal lattice), 3.17–
3.04, 2.70–2.56 (t, 4H, 2CH2CH2CH2–C═O), 2.33–2.29,
2.26–2.23 (t, 4H, 2CH2CH2CH2–C═O), 2.03–1.93, 1.86–
1.59 (m, 4H, 2CH2CH2CH2–C═O), 1.06 (t, 3H, CH3 an
ethanol molecule in the crystal lattice); 13C-NMR
(100 MHz, DMSO-d6), δ ppm: 195.94 (2–C═Ocyclic),
168.68 (C═Oamide), 157.96 (C), 155.71 (CH═N), 154.02,
151.54, 135.71, 134.02, 133.88 (5–C), 130.05, 129.42,
128.28, 127.63, 120.04, 117.32 (8–CH), 111.64, 110.56,
56.50 (3–C), 36.46 (CH2–N), 26.88 (CH), 25.89, 25.80,
25.49, 21.01, 20.40, 19.01 (6–CH2); analysis: calculated
for C28H26N3O4Cl (503.97): C, 66.72; H, 5.21; N,
8.33%. Found: C, 66.84; H, 5.17; N, 8.46%.
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Thangaraj, K.; Leblanc, B. Bioorg Med Chem Lett 2002, 12, 3407.
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Stephen, P. M. Chem Commun 2014, 50, 10222.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet