Synthesis of quinolin-4-yl substituted malonates, cyanoacetates, acetoacetates and related compounds

Article abstract of DOI:10.1002/jhet.5570430118

4-Chloro- or 4-tosyloxyquinolines 1 and 10 react with CH-acidic compounds such as malonates 2a,b, ethyl cyanoacetate (2c), malononitrile (2d), ethyl acetoacetate (2e), acetylacetone (2f) or dimedone (2g) under mild conditions and good yields to quinolin-4

Full text of DOI:10.1002/jhet.5570430118

Jan-Feb 2006
Synthesis of Quinolin-4-yl Substituted Malonates, Cyanoacetates,
Acetoacetates and Related Compounds
117
Wolfgang Stadlbauer*, Anna E. Täubl, Hoai V. Dang, Claudia Reidlinger
and Klaus Zangger
Department of Chemistry, Karl-Franzens University of Graz
Heinrichstrasse 28, A-8010 Graz, Austria/Europe
Received June 16, 2005
4
-Chloro- or 4-tosyloxyquinolines 1 and 10 react with CH-acidic compounds such as malonates 2a,b,
ethyl cyanoacetate (2c), malononitrile (2d), ethyl acetoacetate (2e), acetylacetone (2f) or dimedone (2g)
under mild conditions and good yields to quinolin-4-yl substituted derivatives 3-8 and 11. With 3-phenylsul-
fonylquinolones 1i-k a redox reaction to 2-hydroxy-2-quinolin-4-yl-malonates 9 was observed. Amination
of 3-nitroquinolinyl malonate 3f leads to malonester-amides 13 and 14.
J. Heterocyclic Chem., 43, 117 (2006).
Recently we could show that 3-nitroquinolin-4-yl-mal-
using sodium hydride as the base [2]. It is likely that these
reaction conditions favor already the decomposition reac-
tions we have described earlier in a few examples [1];
however, with our mild reaction conditions 3-nitroquino-
linyl-malonates 3e-j were obtained in yields of 66-95%.
Quinolones 1 having other electron-withdrawing groups in
3-position reacted too in excellent yields to the corre-
sponding malonates 3: in this manner, 4-chloro-3-
cyanoquinolone 1b gave with malonates 2a,b in 85-86%
yield the corresponding quinolinyl-malonates 3a,b; 3-
acetylquinolones 1c,d with 4-tosyloxy substituents as
leaving group gave with diethyl malonate (2a) in 66-69%
yield the corresponding quinolinyl-malonates 3c,d.
When ethyl cyanoacetate (2c) was used as CH-acidic
compound the 3-nitroquinolones 1e-g gave in excellent
yields and short reaction times (3 hours compared with up
to 20 hours in the malonate series [1]) the quinolinyl-
cyanoacetates 4a-c. Malononitrile (2d) reacted with 3-
nitroquinolone 1e to give a very labile compound that
decomposed on work-up. Attempts to purify and identify
the follow-up product were unsuccessful, but it seems
from spectral data (e.g. mass of 239) that a reaction of one
cyano group with the 3-nitro group of the quinolone has
taken place. When the 3,4-dichloroquinolone 1h was
reacted with malononitrile (2d), the expected quinolinyl-
onates, obtained from 4-chloro-3-nitroquinolones and mal-
onates, give in thermal reactions either quinolinylacetates
or a ringclosure reaction to isoxazolo[3,4-c]quinolines [1].
A literature survey revealed that the synthesis of quino-
linyl substituted malonates, cyanoacetates and related CH-
acidic compounds has found great interest either due to
their biological properties or their use as synthons for fur-
ther reactions [2-6]. The synthetic pathways include ring
transformations [6], cine-substitution [3,4], metallation [2]
and substitution with halo-hetaryl compounds, however
the latter one with poor results [2]. In this work we report
on a study about the introduction of 4-quinolinyl sub-
stituents at the CH-acidic carbon of various CH-acidic
compounds. Moreover, the influence of substituents in
position 3 of the quinoline nucleus on this reaction was
studied.
The reaction of ethyl- or methyl malonates 2a,b as CH-
acidic compounds with various 4-chloro- or 4-tosyloxy-2-
quinolones 1b-g in dimethylformamide and potassium car-
bonate as the base, was investigated and found to give
good to excellent yields of 4-quinolinyl substituted mal-
onates 3a-j. It was reported recently that similar 3-nitro-
quinolones give such malonates of type 3 only in poor
yields (8-37%) at reaction temperatures of about 100 °C

1
18
W. Stadlbauer, A. E. Täubl, H. V. Dang, C. Reidlinger and K. Zangger
Vol. 43
malononitrile 5b was obtained in good yield. In the mal-
of the 3-unsubstituted quinolone 1a using a slightly
ononitrile series we were also successful with the reaction
changed reaction protocol: the reaction was carried out in
Scheme 1

Jan-Feb 2006
Synthesis of Quinolin-4-yl Substituted Malonates, Cyanoacetates, Acetoacetates
119
refluxing dimethylformamide (instead of room tempera-
ture) and use of sodium acetate as the base (instead of
potassium carbonate). In this manner, we obtained in 57%
yield the expected quinolinyl-malononitrile 5a.
Malonates 2a,b reacted in good yields with 4-chloro-3-
phenylsulfonylquinolones 1i-k at 60-70 °C to pure, uni-
form products 9a-d. The mass spectra and elemental
analyses of these products were in accordance with struc-
1
The reaction of ethyl acetoacetate (2e) with 3-
cyanoquinolone 1b or 3-nitroquinolones 1e-g gave in
tures corresponding to 3. The H nmr spectra, however,
1
3
did not show any CH-signal of the CH-acidic group. A
C
1
excellent yields quinolinyl-acetoacetates 6a-d. The H
DEPT-135 nmr experiment confirmed the aliphatic CH
2
1
3
and CH carbon atoms. One aliphatic carbon of the 1D 13C
nmr and C nmr spectra spectral data show that these
compounds exist predominantly in the enolized form B
because CH signals disappeared and OH signals can be
3
nmr spectrum at 69.9 ppm was missing and can thereby be
clarified as a quarternary carbon without hydrogen atoms.
According to the shift it has to be bonded to a hetero atom,
most likely an oxygen. All data are in agreement with the
structure of 2-(3-phenylsulfinylquinolin-4-yl)-2-hydroxy-
malonates of structure 9a-d formed by an intra- or inter-
molecular redox-reaction of the phenylsulfonyl com-
pounds. In the literature the oxidation of heterocyclic sub-
stituted malonates to 2-hydroxymalonates has been
described by reaction with bromine or hydrogen peroxide
[7]. Separated signals deriving from diastereotopic sul-
fones could not be detected.
1
13
observed. Both the H and C NMR spectra of 6 showed
two sets of peaks for all protons and carbons, which is
indicative of E/Z isomers at the enolic double bond.
Interestingly, the OH signals at 10.50 (broad singlet) and
1
3.2 ppm (sharp singlet) show the different environment of
the isomers, enabling in the Z-form hydrogen bonding to
the ester carbonyl group. Mass spectra reveal the correct
mass signals; infrared spectra show an ester signal shifted
-
1
to lower frequencies of 1660-1670 cm , together with a
weak OH signal, which indicates again hydrogen bonding
of the enol structure B.
Acetylacetone (2f) gave similarly with 3-cyano-
quinolone 1b or 3-nitroquinolones 1f,g the quinolinyl-sub-
stituted acetylacetones 7a-c. Again the spectral data
revealed that not the diketone structure A but the tau-
Scheme 2
1
tomeric enol structure B is favored: The H nmr spectra do
1
3
not show the CH signal; the C shift of this carbon con-
firms the enolic structure B. In contrast to the acetoacetates
6
, no indication for E/Z isomers could be found. Infrared
spectra show the carbonyl signals at lower frequencies of
660-1670 similar to 6. Mass spectra and elemental analy-
sis confirmed the structures of 7.
,5-Dimethylcyclohexane-1,3-dione (dimedone, 2g) as
1
5
cyclic CH-acidic compound was found to react in the same
manner as the open-chain compounds 2a-f with 4-chloro-
quinolines 1e-g to give in good yields the quinolinyl-sub-
When malonates 2a,b were brought to reaction with 2,4-
dichloroquinolines 10, the reaction took place to give only
monosubstituted quinolinyl-malonates 11a,b. As expected
from former findings in regioselective nucleophilic dis-
placements of 2,4-dichloroquinolines [8], the substitution
in 4-position was assumed. These findings were confirmed
by C nmr spectra: the C-4 signal of the 3-chloro deriva-
tive 10a at 142.6 ppm is shifted in 11a to 140.6 ppm,
whereas the C-2- signal remains nearly unchanged. Similar
findings were obtained with the 3-nitro derivative 10b and
11b: the C-4 signal is shifted from 137.8 to 140.2 ppm.
The reaction conditions were different depending on the
substituent in 3-position of the quinoline: with 3-nitro-
quinolines 10b, already at room temperature the reaction
proceeded smoothly, whereas with 3-chloroquinolines
10a, 60-70 °C was necessary as reaction temperature.
Recently we have studied the thermal behaviour of
diethyl- and dimethyl malonates 3e-j having 3-nitroquino-
linyl substituents [1]. These findings show that depending
1
13
stituted cyclohexanediones 8a-c. The H nmr spectra,
C
DEPT 135 and 2D HMBC experiments again confirm the
1
3
enolized form B of 8. In the C spectrum of 8a two
methyl signals were detected, but the CH groups only
2
1
3
gave rise to a broad C signal around 46 ppm and the eno-
lized cyclohexane carbonyl groups were broadenend
beyond detection. These data can be explained by either a
hindered rotation of the cyclohexene ring caused by the 3-
nitro group of quinoline or a slowed conformational
change of the cyclohexene ring around the C4-C5-C6
1
3
1
3
bonds of the cyclohexene. The broadening of C signals
points to flexibility on the NMR time scale (conforma-
tional exchange rates are in the range of shift differences
-
1
i.e. several 100 s ). Mass spectra of 8a-c confirm the
structures, but only 8a gave correct elemental analysis,
whereas analyses of 8b, c gave deviations of 0.7-0.9%,
although decomposition studies by differential scanning
calorimetry indicated thermal stability up to 270 °C.

120
W. Stadlbauer, A. E. Täubl, H. V. Dang, C. Reidlinger and K. Zangger
Vol. 43
Scheme 3
decomposition signals. The thermal gravimetrical analy-
sis indicates a mass loss of 11%, but the further diagram
does not show a plateau, but a slope. Preparative exper-
ments by heating the compounds 8a-c in diphenylether
to 270-280 °C did not furnish a consistent product, but a
mixture of many compounds. DSC diagrams of 3-nitro-
quinolinyl-acetoacetate 6b and 3-nitroquinolinyl-acetyl-
acetone 7b showed a broad decomposition range at 157
and 229 °C, respectively and were not further investi-
gated. Similarly, 2-(3-phenylsulfinylquinolin-4-yl)-2-
hydroxymalonates 9b,c gave broad decomposition sig-
nals in DSC measurements. Quinolinyl-malonate 11a
showed a decomposition signal at 312 °C in the DSC
diagram which is too high for reasonable thermolytic
reactions. Methyl 3-nitroquinolinyl-malonate 11b, with
a structure similar to 3-nitroquinolinyl-malonates 3f,h,j,
showed two exothermic peaks at 178 and 249 °C, the
first one with a rather high reaction enthalpy of –380
mJ/mg. A preparative experiment, however, by heating
11a to 170-180 °C in diphenylether, yielded a mixture of
many compounds.
on the ester substituent, either a ring closure reaction to
isoxazolo[3,4-c]quinolones took place or quinolinyl-
acetates were formed by decarboxylation. In this report we
studied some amination reactions, which should give mal-
ondiamides. However, when diethyl quinolinylmalonate 3f
was reacted with primary or secondary amines such as
pyridylmethanamines 12a,b or morpholine, even with
excess amines and long reaction times, only malonester-
monoamides 13a,b and 14 were formed.
Scheme 4
Because diethyl- and dimethyl malonates 3e-j have
shown interesting thermal reactions [1], a series of the
compounds obtained in this paper was investigated by
thermoanalytical methods such as differential scanning
calorimetry (DSC) and thermogravimetric analyses
EXPERIMENTAL
Melting points were determined on a Gallenkamp Melting
Point Apparatus, Mod. MFB-595 in open capillary tubes.
Calorimetric data were obtained on a Rheometric Scientific DSC-
Plus instrument with the differential scanning calorimetry soft-
ware Orchestrator V6.5.8. The differential scanning calorimetry
(
TGA) in order to obtain hints for possible thermolytical
reactions. DSC diagrams of 3-nitroquinolinyl-cyclo-
hexenones 8a-c showed sharp, single decomposition
peaks between 268-278 °C with reaction enthalpies
between –570 and – 840 mcal/mg without further
(
DSC) plots were recorded between 25 - 700 °C, with a heating
rate of 2-10 °C/min, and 1.5-3 mg compound in sealed aluminium
crucibles (11 bar). The thermogravimetric analyses (TGA) were
recorded with a Perkin Elmer thermogravimetric analyzer TGA7

Jan-Feb 2006
Synthesis of Quinolin-4-yl Substituted Malonates, Cyanoacetates, Acetoacetates
121
between 30-450 °C with a heating rate of 10°C/min, and 5-12 mg
compound in platinum crucibles, using nitrogen as protective gas.
These compounds were prepared from 3-phenylsulfonyl-4-
hydroxy-2(1H)-quinolones and phosphorylchloride according to
ref. [13].
1
The H nmr spectra were recorded on a Bruker AMX 360 instru-
1
ment (360 MHz H frequency) or on a Bruker Avance DRX 500
13
Dimethyl (3-Cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-
malonate (3a).
1
instrument (500 MHz H frequency). The C nmr-spectra were
13
recorded on a Bruker AMX 360 instrument (90 MHz C fre-
quency) or on a Bruker Avance DRX 500 instrument (125 MHz
C frequency). Chemical shifts are reported in ppm from internal
To a solution of 4-chloro-3-cyanoquinolone 1b (2.18 g, 10
mmol) and dimethyl malonate (2b) (2.64 g, 20 mmol) in
dimethylformamide (40 mL), anhydrous potassium carbonate
(2.8 g, 20 mmol) was added at 20 °C. The mixture was stirred at
room temperature for 3 hours, then poured into ice/water (100
mL) and acidified with conc. hydrochloric acid to pH = 1. After
standing for 12 hours at room temperature, the formed precipitate
was filtered by suction, washed with water until acid-free and
dried. The yield was 2.70 g (86 %) fine brown needles, mp 195
13
tetramethylsilane standard and are given in δ-units. Evaluation of
1
H nmr spectra was performed using the software Mestrec 4.
Infrared spectra were taken on a Mattson Galaxy Series FTIR
7020 instrument in potassium bromide pellets unless otherwise
stated. Elemental analyses were performed on a Fisons elemental
analyzer Mod. EA 1108, and are within ±0.4 of the theoretical
percentages. Mass spectra were taken on a HP 1100 LC/MSD
mass spectral instrument (positive or negative APCI: 50-200 eV,
nitrogen). All reactions were monitored by thin layer chromatog-
raphy, carried out on 0.2 mm silica gel 60 F-254 (Merck) plates
using uv light (254 and 366 nm) for detection. Column chro-
matography was carried out on silica gel (Merck silica gel 60 H).
Common reagent-grade chemicals are either commercially
available and were used without further purification or prepared
by standard literature procedures.
-1 1
°C (ethanol); ir: 2950 w, 2220 s, 1760 s, 1740 s, 1650 s, cm ; H
nmr (CDCl ): δ 3.78 (s, NMe), 3.81 (s, 2 OMe), 5.48 (s, CH),
3
7.33 and 7.74 (2 t, J = 7.1 Hz, 6-H, 7-H), 7.45 (d, J = 7.5 Hz, 8-
H), 7.85 (d, J = 6 Hz, 5-H).
Anal. Calcd. for C H N O : C, 61.14; H, 4.49; N, 8.91.
1
6 14 2 5
Found: C, 61.17; H, 4.36; N, 8.81.
Diethyl (3-Cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-
malonate (3b).
4
-Chloro-1-methyl-3-phenyl-2(1H)-quinolone (1a).
This compound was prepared from 4-chloro-3-cyanoquinolone
1b (2.18 g, 10 mmol) and diethyl malonate (2a) (3.20 g, 20
mmol) according to the procedure described for 3a; the yield was
This compound was prepared from 4-hydroxy-1-methyl-3-
phenyl-2(1H)-quinolone according to ref. [9].
2
3
1
.90 g (85 %) fine pale-yellow needles, mp 151 °C (ethanol); ir:
4
-Chlor-1-methyl-2-oxo-1,2-dihydroquinolin-3-carbonitril (1b).
-
1 1
000 m, 2220 s, 1750 s, 1720 m, 1650 s cm ; H nmr (CDCl ): δ
3
A solution of 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-
-carbonitrile [10] (14.0 g, 70 mmol) in abs. triethylamine (10
.10 (t, J = 7.0 Hz, 2 ethyl-CH ), 3.80 (s, NMe), 4.30 (q, J = 6.0
3
3
Hz, 2 ethyl-CH ), 5.50 (s, CH), 7.30 and 7.70 (2 t, J = 7.1 Hz, 6-
2
mL) and phosphoroxychloride (100 mL) was heated under reflux
for 72 hours. Excess phosphoroxychloride was removed in vacuo
and the residue poured on crushed ice (200 g). The mixture was
neutralized with 6 N sodium hydroxyide solution and the precipi-
tated product filtered by suction and washed with water until acid-
free. The yield was 10.30 g (67 %) light-brown prisms, mp 198-
H, 7-H), 7.50 (d, J = 7.2 Hz, 8-H), 7.90 (d, J = 7 Hz, 5-H); ms:
m/z (%) 343 (20, M+1), 342 (100, M), 270 (57, M – COOEt), 198
(
66, M – 2 COOEt).
Anal. Calcd. for C H N O : C, 63.15; H, 5.30; N, 8.18.
1
8 18 2 5
Found: C, 63.11; H, 5.24; N, 8.17.
-1 1
Diethyl (3-Acetyl-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-
malonate (3c).
2
00 °C (ethanol); ir: 2220 s, 1640 s, 1610s cm ; H nmr (CDCl ):
3
δ 3.65 (s, NMe), 7.49 (t, J = 7.3 Hz, 1 ArH), 7.73 (d, J = 8.6 Hz, 8-
H), 7.91 (t, J = 7.2 Hz, 1 ArH), 8.07 (d, J = 7.4 Hz, 5-H).
This compound was prepared from 3-acetyl-4-tosy-
loxyquinolone 1c (3.71 g, 10 mmol) and diethyl malonate (2a)
Anal. Calcd. for C H ClN O: C, 60.43; H, 3.23; N, 12.81.
11
7
2
Found: C, 60.12; H, 3.46; N, 12.56.
(
3.20 g, 20 mmol) according to the procedure described for 3a
(
20 hours reaction time); the yield was 2.27 g (69 %) colorless
3
-Acetyl-1-methyl-4-tosyloxy-2(1H)-quinolone (1c) and 3-
microprisms, mp 128 °C (ethanol); ir: 3000 m, 1760 s, 1730 s,
1
ethyl-CH ), 2.60 (s, Me), 3.70 (s, NMe), 4.18-4.26 (m, 2 ethyl-
CH ), 5.00 (s, CH), 7.25 and 7.60 (2 t, J = 7.1 Hz, 6-H, 7-H), 7.40
Acetyl-1-phenyl-4-tosyloxy-2(1H)-quinolone (1d).
-
1 1
700 s, 1650 m cm ; H nmr (CDCl ): δ 1.20 (t, J = 7.0 Hz, 2
3
These compounds were prepared from 3-acetyl-4-hydroxy-
(1H)-quinolones and tosylchloride according to ref. [11].
3
2
2
(
d, J = 8.5 Hz, 8-H), 7.86 (d, J = 8.0 Hz, 5-H).
Anal. Calcd. for C19H21NO : C, 63.50; H, 5.89; N, 3.90.
4
-Chloro-1-methyl-3-nitro-2(1H)-quinolone (1e), 4-Chloro-1-
phenyl-3-nitro-2(1H)-quinolone (1f) and 1-Chloro-2-nitro-6,7-
dihydro-benzo[ij]quinolizin-3-one (1g).
6
Found: C, 63.12; H, 5.89; N, 4.13.
These compounds were prepared from 4-hydroxy-3-nitro-
Diethyl (3-Acetyl-2-oxo-1-phenyl-1,2-dihydroquinolin-4-yl)-
2
(1H)-quinolones and phosphoryl chloride according to ref. [12].
malonate (3d).
3
,4-Dichloro-1-methyl-2(1H)-quinolone (1h).
This compound was prepared from 3-acetyl-4-tosy-
loxyquinolone 1d (2.30 g, 5 mmol) and diethyl malonate (2a)
1.60 g, 10 mmol) according to the procedure described for 3a
13 hours reaction time); the yield was 1.40 g (66 %) light yellow
This compound was prepared from 3-chloro-4-hydroxy-2(1H)-
(
(
quinolone and phosphoryl chloride according to ref. [8].
4
4
-Chloro-1-methyl-3-phenylsulfonyl-2(1H)-quinolone (1i),
-Chloro-1-phenyl-3-phenylsulfonyl-2(1H)-quinolone (1j)
needles, mp 134.8 °C (ethanol); ir: 2940 m, 1760 s, 1740 s, 1650
-
1 1
m cm ; H nmr (CDCl ): δ 1.25 (t, J = 7.0 Hz, 2 ethyl-CH ),
3
2
and 1-Chloro-2-phenylsulfonyl-6,7-dihydro-benzo[ij]quino-
lizin-3-one (1k).
2.65 (s, Me), 4.20-435 (m, 2 ethyl-CH ), 5.20 (s, CH), 6.70 (d, J
2
= 7.5 Hz, 8-H), 7.20-7.40 (m, 4 ArH), 7.55-7.70 (m, 3 ArH), 7.90

122
W. Stadlbauer, A. E. Täubl, H. V. Dang, C. Reidlinger and K. Zangger
Vol. 43
(
3
d, J = 8.1 Hz, 5-H); ms: m/z (%) 422 (34, M+1), 421 (100, M),
76 (16), 304 (20).
Anal. Calcd. for C24H23NO : C, 68.40; H, 5.50; N, 3.32.
(40 mL), anhydrous sodium acetate (1.64 g, 20 mmol) was added
at 20 °C. The mixture was heated under reflux for 12 hours and
then poured into ice/water (100 mL). After standing for 12 hours
at room temperature, the formed precipitate was filtered by suc-
tion, washed with water and dried. The yield was 1.62 g (57%)
brownish prisms, mp 252 °C (ethanol); ir: 3065-2592 s, 2207 s,
6
Found: C, 68.64; H, 5.79; N, 3.23.
Dimethyl (1-Methyl-3-nitro-2-oxo-1,2-dihydroquinolin-4-
yl)malonate (3e), Diethyl (1-Methyl-3-nitro-2-oxo-1,2-dihydro-
quinolin-4-yl)malonate (3f), Dimethyl (3-Nitro-2-oxo-1-phenyl-
1
1
Nitro-3-oxo-6,7-dihydro-3H,5H-benzo[ij]quinolizin-4-yl)mal-
onate (3i) and Diethyl (2-Nitro-3-oxo-6,7-dihydro-3H,5H-
benzo[ij]quinolizin-4-yl)malonate (3j).
-1 1
2
6
5
180 s, 1605 s, 1591 s cm ; H nmr (DMSO-d ): δ 6.34 (s, CH),
6
.67 (d, J = 8.4 Hz, 1 ArH), 7.34-7.40 (m, 3 ArH), 7.50 -7.62 (m,
,2-dihydroquinolin-4-yl)malonate (3g), Diethyl (3-Nitro-2-oxo-
-phenyl-1,2-dihydroquinolin-4-yl)malonate (3h), Dimethyl (2-
PhH), 8.82 (d, J = 8.0 Hz, 5-H); ms: m/z (%) 286 (8, M+1), 285
(
100, M), 278 (24), 260 (37, M–25).
Anal. Calcd. for C H N O: C, 75.78; H, 3.89; N, 14.73.
1
8 11 3
Found: C, 75.39; H, 3.28; N, 14.34.
1-Methyl-3-chloro-2-oxo-1,2-dihydroquinolin-4-yl)malononi-
trile (5b).
This compound was prepared from 1-chloroquinolone 1h
1.14 g, 5 mmol) and malonodinitrile (2d) (0.66 g, 10 mmol)
(
These compounds were prepared from 4-chloro-3-nitro-
quinolones 1e,f and 1-chloro-2-nitro-benzoquinolizinone (1g)
with malonates 2a,b according to ref. [1].
(
Ethyl Cyano-(1-methyl-3-nitro-2-oxo-1,2-dihydroquinolin-4-
yl)acetate (4a).
according to the procedure described for 3a (5 hours reaction
time); the yield was 1.00 g (78%) light-brown prisms, mp 180 °C
-1
This compound was prepared from 4-chloro-3-nitroquinolone
e (2.39 g, 10 mmol) and ethyl cyanoacetate (2c) (2.26 g, 20
(ethanol); ir: 3461m, 2939 s, 2207 s, 1657 s, 1609 s, 1595 s cm ;
1
1
H nmr (CDCl ): δ 3.87 (s, Me), 6.14 (s, CH), 7.55 (q, J = 8.0 Hz,
3
mmol) according to the procedure described for 3a (3 hours reac-
2 ArH), 7.79 (t, J = 7.6 Hz, 1 ArH), 8.06 (d, J = 7.8 Hz, 5-H); ms:
tion time); the yield was 3.02 g (95 %) orange microprisms, mp
m/z (%) 259 (40, M+2), 257 (100, M).
-
1 1
1
61 °C (ethanol); ir: 2900 m, 2260 m, 1750 s, 1660 s cm ; H
Anal. Calcd. for C H N O : C, 60.60; H, 3.13; N, 16.31.
13 8 4 3
nmr (CDCl ): δ 1.30 (t, J = 7 Hz, ethyl-CH ), 3.81 (s, NMe), 4.2-
Found: C, 60.61 H, 3.02; N, 16.15.
3
3
4
.4 (m, ethyl-CH ), 5.10 (s, CH), 7.42-7.63 (m, 2 ArH), 7.81 (d, J
2
Ethyl 2-(3-Cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-3-
oxobutanoate (6a).
=
7.1 Hz, 8-H), 8.02 (d, J = 7.0 Hz, 5-H); ms: m/z (%) 316 (21,
M+1), 315 (M, 100), 246 (19), 188 (28), 174 (67).
Anal. Calcd. for C H N O : C, 57.14; H, 4.16; N, 13.33.
Found: C, 56.26; H, 4.18; N, 12.86.
This compound was prepared from 4-chloro-3-cyanoquinolone
1b (2.18 g, 10 mmol) and ethyl acetoacetate (2e) (2.60 g, 20 mmol)
according to the procedure described for 3a (3 hours reaction
time); the yield was 2.69 g (86 %) lightbrown needles, mp 170 °C
1
5 13 3 5
Ethyl Cyano-(3-nitro-2-oxo-1-phenyl-1,2-dihydroquinolin-4-
yl)acetate (4b).
-1 1
(ethanol); ir: 3000 m, 2220 s, 1650 s, 1620 m 1550 s cm ; H nmr
This compound was prepared from 4-chloro-3-nitroquinolone
f (3.00 g, 10 mmol) and ethyl cyanoacetate (2c) (2.26 g, 20
(DMSO-d ): δ 0.96 and 1.03 (2 t, J = 7.1 Hz, ethyl-CH ), 1.82 and
6
3
1
2.56 (2 s, Me), 3.68 and 3.69 (s, NMe), 4.01 and 4.11 (2 q, J = 7.2
mmol) according to the procedure described for 3a (4 hours reac-
Hz, ethyl-CH ), 7.34 and 7.36 (2 t, J = 7.0 Hz, 7-H), 7.60 and 7.62
2
tion time); the yield was 3.60 g (95 %) yellow microprisms, mp
(2 t, J = 7.0 Hz, 6-H), 7.66 and 7.68 (2 d, J = 7.0 Hz, 8-H), 7.79 and
7.81 (2 d, J = 7.1 Hz, 5-H), 11.20 and 13.16 (2 s, OH); C nmr
-
1
1
13
1
43 °C (ethanol); ir: 2900 m, 2260 m, 1760 s, 1680 s cm ; H
nmr (DMSO-d ): δ 1.32 (t, J = 7.1 Hz, ethyl-CH ), 4.25-4.40 (m,
(DMSO-d ): δ 14.4 and 14.6 (ethyl-CH ), 20.1 and 20.2 (Me),
6
3
6
3
ethyl-CH ), 5.21 (s, CH), 6.91 (d, J = 7.2 Hz, 8-H), 7.32-7.61 (m,
30.3 and 30.5 (NMe), 59.8 and 61.6 (OCH ), 97.4 and 99.9 (C-2 of
2
2
7
ArH), 8.02 (d, J = 7.1 Hz, 5-H).
acetoacetate), 115.9-157.0 (ArC and CN), 158.8 (amide-CO),
165.5 and 170.0 (ester-CO), 171.3 and 176.2 (enol-C).
Anal. Calcd. for C H N O : C, 63.66; H, 4.01; N, 11.14.
2
0 15 3 5
Found: C, 63.56; H, 4.02; N, 10.93.
Anal. Calcd. for C17H N O : C, 65.38; H, 5.16; N, 8.97.
16 2 4
Found: C, 65.31; H, 5.07; N, 8.89.
Ethyl Cyano-(2-nitro-3-oxo-6,7-dihydro-3H,5H-benzo[ij]quino-
lizin-1-yl)-acetate (4c).
Ethyl 2-(1-Methyl-3-nitro-2-oxo-1,2-dihydroquinolin-4-yl)-3-
oxobutanoate (6b).
This compound was prepared from 1-chloro-2-nitrobenzo-
quinolizinone 1g (2.65 g, 10 mmol) and ethyl cyanoacetate (2c)
This compound was prepared from 4-chloro-3-nitroquinolone
1e (2.38 g, 10 mmol) and ethyl acetoacetate (2e) (2.60 g, 20 mmol)
in dimethylsulfoxide (40 mL) according to the procedure described
for 3a (5 hours reaction time); the yield was 3.04 g (90 %) yellow
microprisms, mp 148-150 °C (ethanol); calorimetric data for ther-
molysis: mp onset 147.7 °C, peak maximum 150.0 °C, ∆H = 16
mcal/mg; decomposition onset 157.4 °C, peak maximum 163.1 °C,
(
2.26 g, 20 mmol) according to the procedure described for 3a (4
hours reaction time); the yield was 3.26 g (96 %) brown micro-
prisms, mp 145 °C (ethanol); ir: 2900 m, 2260 m, 1750 s, 1650 s
-
1 1
cm ; H nmr (DMSO-d ): δ 1.10 (t, J = 7.0 Hz, ethyl-CH ),
6
3
2
.00-2.15 (m, CH ), 3.00 (t, J = 7.1 Hz, Ar-CH ), 4.10-4.30 (m,
2
2
ethyl-CH and NCH ), 6.50 (s, CH), 7.35-7.51 (m, 9-H), 7.60 (d,
2
2
-1 1
J = 7.2 Hz, 8-H), 7.85 (d, J = 7 Hz, 10-H).
∆H = –13 mcal/mg; ir: 3000 m, 1670 s, 1600 m, 1540 s cm ; H
Anal. Calcd. for C H N O : C, 59.82; H, 4.43; N, 12.31.
nmr (CDCl ): δ 1.10 and 1.12 (2 t, J = 6.1 Hz, ethyl-CH ), 1.90 and
1
7
15
3
5
3
3
Found: C, 59.77; H, 4.50; N, 12.01.
2.60 (2 s, Me), 3.90 and 3.92 (2 s, NMe), 4.00-4.35 (m, ethyl-
CH ), 7.40 and 7.42 (2 t, J = 6.3 Hz, 1 ArH), 7.45 and 7.47 (2 d, J
2
(
2-Oxo-1-phenyl-1,2-dihydroquinolin-4-yl)malononitrile (5a).
To a solution of 1-chloroquinolone 1a (2.55 g, 10 mmol) and
=
7.0 Hz, 8-H), 7.60-7.80 (m, 2 ArH), 11.50 and 13.25 (2 s, OH);
13
C nmr (DMSO-d ): δ 14.3 and 14.6 (ethyl-CH ), 20.1 and 20.2
6
3
malonodinitrile (2d) (0.66 g, 10 mmol) in dimethylformamide
(Me), 30.5 and 30.7 (NMe), 59.7 and 61.6 (OCH ), 97.5 and 100.0
2

Jan-Feb 2006
Synthesis of Quinolin-4-yl Substituted Malonates, Cyanoacetates, Acetoacetates
123
(
C-2 of acetoacetate), 116.1-149.0 (ArC and CN), 159.0 (amide-
CO), 165.0 and 170.0 (ester-CO), 171.0 and 176.0 (enol-C).
Anal. Calcd. for C H N O : C, 57.83; H, 4.85; N, 8.43.
6.85 (d, J = 8.5 Hz, 1 ArH), 7.35-7.39 (m, 3 ArH), 7.53 (t, J = 7.3
1
3
Hz, 1 ArH), 7.58-7.69 (m, 4 ArH); C nmr (DMSO-d ): δ 24.2
6
(Me), 104.1 (C-3 of acetylacetone), 117.0-143.6 (ArC), 154.2
(amide-CO), 191.1 (enol-C).
1
6 16 2 6
Found: C, 57.99, H, 4.87; N, 8.40.
Anal. Calcd. for C H N O : C, 65.93; H, 4.43; N, 7.69.
Found: C, 65.75; H, 4.46; N, 7.56.
2
0 16 2 5
Ethyl 2-(3-Nitro-2-oxo-1-phenyl-1,2-dihydroquinolin-4-yl)-3-
oxobutanoate (6c).
3
-(2-Nitro-3-oxo-6,7-dihydro-3H,5H-benzo[ij]quinolizin-1-
This compound was prepared from 4-chloro-3-nitroquinolone
f (3.01 g, 10 mmol) and ethyl acetoacetate (2e) (2.60 g, 20
yl)pentan-2,4-dione (7c).
1
mmol) in dimethylsulfoxide (40 mL) according to the procedure
described for 3a (5 hours reaction time); the yield was 3.86 g (98
This compound was prepared from 1-chloro-2-nitrobenzo-
quinolizinone 1g (2.65 g, 10 mmol) and acetylacetone (2f) (2.05
g, 20 mmol) according to the procedure described for 3a (4 hours
reaction time); the yield was 2.68 g (82 %), yellow microprisms,
%
) lightbrown needles, mp 176 °C (ethanol); ir: 3000 w, 1670 s,
-1 1
1640 s, 1530 s cm ; H nmr (CDCl ): δ 1.10 and 1.12 (2 t, J =
6.0 Hz, ethyl-CH ), 1.95 and 2.60 (2 s, Me), 4.05 and 4.15 (2 m,
3
-1 1
mp 171 °C (ethanol); ir: 2900 w, 1660 s, 1600 s, 1540 s cm ; H
3
ethyl-CH ), 6.80 and 6.82 (d, J = 6.1 Hz, 1 ArH), 7.30-7.70 (m, 8
ArH), 11.50 and 13.30 (2 s, OH); ms: m/z (%) 395 (15, M+1),
nmr (CDCl ): δ = 1.90 (s, 2 Me), 2.05-2.20 (m, CH ), 3.00-3.10
2
3
2
(m, ArCH ), 4.15-4.25 (m, NCH ), 7.35 (t, J = 6.0 Hz, 1 ArH),
2
2
3
94 (100%, M), 334 (14), 237 (37).
Anal. Calcd. for C H N O : C, 63.96; H, 4.60; N, 7.10.
7.55-7.70 (m, 2 ArH).
Anal. Calcd. for C H N O : C, 62.19; H, 4.91; N, 8.53.
2
1
18
2
6
17 16 2 5
Found: C, 64.00; H, 4.58; N, 7.10.
Found: C, 62.34; H, 4.92; N, 8.49.
Ethyl 2-(2-Nitro-3-oxo-6,7-dihydro-3H,5H-benzo[ij]quinolizin-
4-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-1-methyl-
1
-yl)-3-oxobutanoate (6d).
3-nitroquinolin-2(1H)-one (8a).
This compound was prepared from 1-chloro-2-nitro-benzo-
This compound was prepared from 4-chloro-3-nitroquinolone
1e (2.38 g, 10 mmol) and dimedone (2g) (2.10 g, 15 mmol) accord-
ing to the procedure described for 3a (5 hours reaction time); the
yield was 3.00 g (88 %), colorless microprisms, mp. 283 °C dec.
(dimethylformamide); calorimetric data for thermolysis: decompo-
sition onset 278.1 °C, peak maximum 283.6 °C, ∆H = –686
quinolizinone 1g (2.65 g, 10 mmol) and ethyl acetoacetate (2e)
2.60 g, 20 mmol) in dimethylsulfoxide (40 mL) according to the
procedure described for 3a (3 hours reaction time); the yield was
.04 g (85 %) light yellow needles, mp 132 °C (ethanol/water);
(
3
-
1 1
ir: 2800-3000 w, 1660 s, 1600 s cm ; H nmr (DMSO-d ): δ 1.02
6
-1 1
and 1.04 (2 t, J = 7.2 Hz, 2 ethyl-CH ), 1.70 and 2.60 (2 s, Me),
mJ/mg; ir: 3100 br, 1660 s, 1600 m 1540 s cm ; H nmr (DMSO-
3
2
.10-2.20 (m, CH ), 3.00-3.10 (m, ArCH ), 4.05-4.20 (m, ethyl-
d ): δ = 1.01 (s, Me), 1.13 (s, Me), 2.27 (d, J = 7.0 Hz, CH ), 2.57
2
2
6
2
CH and NCH ), 7.25-7.35 (m, 1 ArH), 7.45-7.60 (m, 2 ArH),
(d, J = 7.0 Hz, CH ), 3.73 (s, NMe), 7.34 (t, J = 6.1 Hz, 7-H), 7.53
2
2
2
1
1.50 and 13.10 (2 s, OH).
(d, J = 6.0 Hz, 8-H), 7.67 (t, J = 6.5 Hz, 6-H), 7.75 (d, J = 6.5 Hz, 8-
13
Anal. Calcd. for C H N O : C, 60.33; H, 5.06; N, 7.82.
H), 11.60 (s, OH, exchangeable with D O); C nmr (DMSO-d6):
1
8
18
2
6
2
Found: C, 60.34; H, 5.16; N, 7.70.
δ 26.8 and 29.7 (dimedone-Me), 30.5 (NMe), 32.1 (dimedone-C5),
54.0 (dimedone-CH ), 105.9 (dimedone-C2), 116.0-143.5 (ArC),
2
4
-(2,4-Dioxopent-3-yl)-1-methyl-2-oxo-1,2-dihydroquinolin-3-
1
1
(
54.4 (amide-CO); H nmr of dimedone (2g) (DMSO-d ): δ 0.98
6
carbonitrile (7a).
s, 2 Me), 2.11 (s, 2 CH ), 5.18 (s, 2-H as enol), 10.97 (s, OH); ms:
2
This compound was prepared from 4-chloro-2-cyanoquinolone
m/z (%) 343 (23, M+1), 342 (100, M), 296 (10, M – NO2).
Anal. Calcd. for C H N O : C, 63.15; H, 5.30; N, 8.18.
1
b (2.18 g, 10 mmol) and acetylacetone (2f) (2.05 g, 20 mmol)
1
8 18 2 5
according to the procedure described for 3a (3 hours reaction
time); the yield was 2.24 g (79 %) fine light yellow needles, mp
Found: C, 62.78; H, 5.34; N, 8.24.
4
-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3-nitro-1-
-
1
;
67 °C (ethanol); ir: 3000 w, 2220 s, 1650 s, 1610 m 1550 m, cm
phenylquinolin-2(1H)-one (8b).
1
1
H nmr (CDCl ): δ 1.93 (s, 2 Me), 3.83 (s, NMe), 7.37 (t, J =
3
7
.1 Hz, 1 ArH), 7.51 (d, J = 7.0 Hz, 8-H), 7.66 (t, J = 7.1 Hz,
This compound was prepared from 4-chloro-3-nitroquinolone
1f (3.01 g, 10 mmol) and dimedone (2g) (2.10 g, 15 mmol)
according to the procedure described for 3a (5 hours reaction
time); the yield was 3.95 g (98 %), colorless microprisms, mp
273 °C dec (1-propanol); calorimetric data for thermolysis:
decomposition onset 268.1 °C, peak maximum 273.4 °C, ∆H =
1
3
ArH), 7.80 (d, J = 7.2 Hz, 5-H); C nmr (DMSO-d ): δ 23.9
6
(
(
Me), 30.5 (NMe), 108.3 (C-3 of acetylacetone), 109.5-154.5
ArC and CN), 158.6 (amide-CO), 190.9 (enol-C); ms: m/z (%)
2
83 (20, M+1), 282 (100, M), 241 (26), 198 (38).
Anal. Calcd. for C H N O : C, 68.08; H, 5.00; N, 9.92.
1
6 14 2 3
-1
Found: C, 67.81; H, 5.01; N, 9.92.
–573 mJ/mg; ir: 3300 br, 3000 m, 1660 s, 1630 m, 1530 s cm ;
1
H nmr (DMSO-d ): δ = 1.07 (s, Me), 1.16 (s, Me), 2.30 and
6
3
-(3-Nitro-2-oxo-1-phenyl-1,2-dihydroquinolin-4-yl)pentan-2,4-
2
.40 (2 s, 2 CH ), 6.70 (d, J = 7.0 Hz, 1 Ar), 7.20-7.60 (m, 8
2
dione (7b).
ArH), 11.60 (s, b, OH); ms: m/z (%) 405 (34, M+1), 404 (100,
M), 358 (5, M – NO2).
This compound was prepared from 4-chloro-3-nitroquinolone
1
f (0.90 g, 3 mmol) and acetylacetone (2f) (0.70 g, 7 mmol)
Anal. Calcd. for C H N O : C, 68.31; H, 4.98; N, 6.93.
2
3 20 2 5
according to the procedure described for 3a (3 hours reaction
time); the yield was 0.83 g (96 %), greenish microprisms, mp 202
Found: C, 67.60; H, 4.98; N, 5.99.
1
6
-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-2-nitro-
,7-dihydro-5H-benzo[ij]quinolizin-3-one (8c).
°
°
C (ethanol); calorimetric data for thermolysis: mp onset 197.5
C, peak maximum 202.0 °C, ∆H = 88 mJ/mg; decomposition
onset 229.0 °C, peak maximum 259.6 °C, ∆H = –723 mJ/mg; ir:
1
This compound was prepared from 1-chloro-2-nitrobenzo-
quinolizinone 1g (2.64 g, 10 mmol) and dimedone (2g) (2.10 g,
-1 1
670 s, 1600 s, 1540 s cm ; H nmr (CDCl ): δ 2.03 (s, 2 Me),
3

124
W. Stadlbauer, A. E. Täubl, H. V. Dang, C. Reidlinger and K. Zangger
Vol. 43
1
5 mmol) according to the procedure described for 3a (5 hours
onate (2b) (1.10 g, 8 mmol) according to the procedure described
for 9a; the yield was 1.01 g (61 %) beige microprisms, mp 197 °C
(ethanol); calorimetric data for thermolysis: mp onset 191.7 °C,
peak maximum 196.6 °C, ∆H = 16 mcal/mg; decomposition
onset 258.6 °C, peak maximum 279.8 °C, ∆H = –10 mcal/mg; ir:
reaction time); the yield was 3.31 g (90 %), colorless micro-
prisms, mp 278 °C dec (ethanol); calorimetric data for thermoly-
sis: decomposition onset 272.4 °C, peak maximum 277.6 °C, ∆H
-1 1
=
–848 mJ/mg; ir: 3000 w, 1660 s, 1590 m cm ; H nmr (DMSO-
-1 1
d ): δ 1.00 (s, Me), 1.10 (s, Me), 2.20 (s, 2 CH ), 2.40-2.60 (m, 2
2900 m, 1760 s, 1730 s, 1640 s cm ; H nmr (DMSO-d ): δ 1.90
6
2
6
CH ), 3.00 (m, Ar-CH ), 4.10 (m, NCH ), 7.05-7.15 (m, 1 ArH),
(m, CH ), 2.91-2.94 (m, Ar-CH ), 3.62 (s, 2 MeO), 3.86-89 (m,
2
2
2
2 2
7
(
–
.30 (d, J = 6.0 Hz, 1 ArH), 7.50 (d, J = 6.1 Hz, 1 H, ArH), 11.50
s, b, OH); ms: m/z (%) 369 (23, M+1), 368 (100, M), 322 (5, M
NO2).
Anal. Calcd. for C H N O : C, 65.21; H, 5.47; N, 7.60.
N-CH ), 7.27 (t, J = 7.5 Hz, 1 Aryl-H), 7.50-7.70 (m, 6 ArH),
7.92 (d, J = 7.5 Hz, 5-H).
2
Anal. Calcd. for C H NO S: C, 60.65; H, 4.65; N, 3.08.
23
21
7
Found: C, 60.48; H, 4.66; N, 3.01.
2
0 20 2 5
Found: C, 64.83; H, 5.36; N, 8.40.
Diethyl 2-Hydroxy-2-(3-oxo-2-phenylsulfinyl-6,7-dihydro-5H-
benzo[ij]quinolizin-1-yl)malonate (9d).
Diethyl 2-Hydroxy-2-(1-methyl-2-oxo-3-phenylsulfinyl-1,2-
dihydroquinolin-4-yl)malonate (9a).
This compound was prepared from 1-chloro-2-phenylsulfonyl-
benzoquinolizinone 1k (1.79 g, 5 mmol) and diethyl malonate (2a)
(1.60 g, 10 mmol) according to the procedure described for 9a (4
hours reaction time); the yield was 1.89 g (78 %), fine yellow nee-
To a solution of 4-chloro-3-phenylsulfonylquinolone 1i (1.67
g, 5 mmol) and diethyl malonate (2a) (1.60 g, 10 mmol) in
dimethylformamide (40 mL), anhydrous potassium carbonate
-
(
6
2.8 g, 20 mmol) was added at 20 °C. The mixture was stirred at
0-70 °C for 4 hours, then poured into ice/water (100 mL) and
acidified with 6 M hydrochloric acid to pH = 1. After standing for
2 hours at room temperature, the formed precipitate was filtered
dles, mp. 177 °C (ethanol); ir: 3000 m, 1780 s, 1730 m, 1640 s, cm
1
1
; H nmr (CDCl ): δ 1.25 (t, J = 6.4 Hz, 2 ethyl-CH ), 2.10 (m,
3
3
CH ), 3.00 (t, J = 6.1 Hz, Ar-CH ), 4.05 (t, J = 6.2 Hz, N-CH ),
2
2
2
1
4.20-4.45 (m, 2 ethyl-CH ), 7.10 (t, J = 6.5 Hz, 1 ArH), 7.40 (d, J =
2
by suction, washed with water until acid-free and dried. The yield
was 1.83 g (80 %) orange microprisms, mp 283 °C (ethanol); ir:
6.1 Hz, 1 ArH), 7.45-7.65 (m, 3 PhH), 7.75 (d, J = 6 Hz, 1 ArH),
8.10 (d, J = 6.0 Hz, 2 ArH); ms: m/z (%) 484 (27, M+1), 483 (100,
M), 411 (39, M – COOEt), 339 (83, M – 2 COOEt).
-1 1
3
7
300 m, 1660 s, 1540 s cm ; H nmr (DMSO-d ): δ 0.91 (t, J =
6
.0 Hz, 2 ethyl-CH ), 3.43 (s, NMe), 3.75 (q, J = 7.1 Hz, 2 ethyl-
Anal. Calcd. for C H NO S: C, 62.10; H, 5.21; N, 2.90.
3
25 25 7
CH ), 7.18 (t, J = 7.2 Hz, 8-H), 7.35-7.50 (m, 4 ArH), 7.58 (t, 2
Gef.: C, 62.18; H, 5.01; N, 2.84.
,3,4-Trichloroquinoline and (10a) 2,4-Dichloro-3-nitroquino-
2
1
3
ArH), 7.79 (d, J = 7.1 Hz, 2 ArH), 8.03 (d, J = 7.2 Hz, 5-H);
C
2
nmr (DMSO-d ): δ 15.5 (ethyl-CH ), 29.3 (NMe), 56.2 (ethyl-
6
3
line (10b).
CH ; inversion by DEPT-135 experiment), 69.9 (quartery mal-
2
onyl-C; missing in DEPT-135 experiment), 114.6 (Ar-CH), 121.7
These compounds were synthesized according to ref. [8].
Diethyl 2-(2,3-Dichloroquinolin-4-yl)malonate (11a).
(Ar-CH), 123.8 (Ar-C), 126.7 (Ar-C), 127.4 (Ar-CH), 128.3 (Ar-
CH), 130.4 (Ar-CH), 132.1 (Ar-CH), 132.3 (Ar-CH), 140.3 (Ar-
C), 144.9 (Ar-C), 157.9 (SO-C), 158.6 (ester-C=O), 166.3
To a solution of 2,3,4-trichloroquinoline (10a) (1.66 g, 5
mmol) and diethyl malonate (2a) (1.60 g, 10 mmol) in dimethyl-
formamide (40 mL), anhydrous potassium carbonate (2.8 g, 20
mmol) was added at 20 °C. The mixture was stirred at 60 °C for 4
hours, then poured into ice/water (100 mL) and acidified with
conc. hydrochloric acid to pH = 1. After standing for 12 hours at
room temperature, the formed precipitate was filtered by suction,
washed with water until acid-free and dried. The yield was
0.85 g (48 %), colorless prisms, mp. 103 °C (ethanol); calori-
metric data for thermolysis: mp onset 100.3 °C, peak maximum
103.0 °C, ∆H = 46 mJ/mg; decomposition onset 305.4 °C, peak
maximum 312.2 °C, ∆H = –326 mJ/mg; ir: 2980 s, 1760 s, 1750 s
(
(
amide-C=O); ms: m/z (%) 458 (15, M+1), 457 (100, M), 385
40, M – COOEt), 313 (89, M – 2 COOEt).
Anal. Calcd. for C H NO S: C, 60.38, H, 5.07; N, 3.06.
2
3
23
7
Found: C, 60.02, H, 5.34; N, 3.38.
Diethyl 2-Hydroxy-2-(2-oxo-1-phenyl-3-phenylsulfinyl-1,2-
dihydroquinolin-4-yl)malonate (9b).
This compound was prepared from 4-chloro-3-phenylsul-
fonylquinolone 1j (1.98 g, 5 mmol) and diethyl malonate (2a)
(
1.60 g, 10 mmol) according to the procedure described for 9a;
the yield was 1.97 g (76 %) pale yellow microprisms, mp 122 °C
ethanol); calorimetric data for thermolysis: mp onset 116.6 °C,
-
1 1
(
cm ; H nmr (CDCl ): δ 1.20 (t, J = 7.0 Hz, 2 Me), 4.25 (q, J =
3
peak maximum 122.0 °C, ∆H = 11 mcal/mg; decomposition
7.1 Hz, 2 CH ), 5.80 (s, CH), 7.60 (t, J = 7.0 Hz, 1 ArH), 7.75 (t,
2
onset 247.0 °C, peak maximum 276.7 °C, ∆H = –14 mcal/mg; ir:
J = 7.1 Hz, 1 ArH), 7.95 (d, J = 7.2 Hz, 1 ArH), 8.05 (d, J = 5.0
-
1 1
13
2
950 m, 1730 s, 1660 s, cm ; H nmr (CDCl ): δ 1.35 (t, J = 7.0
Hz, 1 ArH); C nmr (CDCl ): δ 15.1 (Me), 46.8 (CH), 58.3
3
3
Hz, 2 ethyl-CH ), 4.20-4.45 (m, 2 ethyl-CH ), 6.65 (d, J = 7.1
(CH ), 122.9 (Ar-CH), 126.1 (Ar-CH), 127.8 (Ar-CH), 128.0
3
2
2
Hz, 8-H), 7.10-7.30 (m, 3 ArH), 7.30-7.70 (m, 8 ArH), 7.95 (d, J
7.1 Hz, 1 ArH), 8.10 (d, J = 7.0 Hz, 5-H); ms: m/z (%) 520 (32,
(Ar-CH), 130.5 (Ar-CH), 140.6 (C-4), 145.5 (C-8a), 147.6 (C-2),
158.6 (ester-C=O).
=
M+1), 519 (100, M), 447 (39, M – COOEt), 375 (76, M – 2
COOEt).
Anal. Calcd. for C H Cl NO : C, 53.95; H, 4.24; N, 3.93.
Found: C, 53.96; H, 4.14; N, 3.86.
16 15 2 4
Anal. Calcd. for C H NO S: C, 64.73; H, 4.85; N, 2.70.
Found: C, 64.72; H, 4.61; N, 2.65.
2
8
25
7
Dimethyl 2-(2-Chloro-3-nitroquinolin-4-yl)malonate (11b).
This compound was prepared from 2,4-dichloro-3-nitroquino-
line (10b) (1.21 g, 5 mmol) and dimethyl malonate (2b) (1.60 g,
0 mmol) according to the procedure described for 3a (5 hours
Dimethyl 2-Hydroxy-2-(3-oxo-2-phenylsulfinyl-6,7-dihydro-
5H-benzo[ij]quinolizin-1-yl)malonate (9c).
1
This compound was prepared from 1-chloro-2-phenylsulfonyl-
reaction time); the yield was 1.04 g (61 %), colorless needles, mp
benzoquinolizinone 1k (1.30 g, 3.6 mmol) and dimethyl mal-
152 °C (ethanol); calorimetric data for thermolysis: mp onset

Jan-Feb 2006
Synthesis of Quinolin-4-yl Substituted Malonates, Cyanoacetates, Acetoacetates
125
1
46.1 °C, peak maximum 151.8 °C, ∆H = 75 mJ/mg; decomposi-
the method described for 13a; the yield was 1.57 g (78 %) light
tion onset 170.6 °C, peak maximum 178.6 °C, ∆H = –378 mJ/mg;
yellow prisms, mp 91 °C (toluene); ir: 2900 m, 1740 s, 1650 s,
-
1 1
decomposition onset 249.1 °C, peak maximum 268.6 °C, ∆H =
1540 s cm ; H nmr (CDCl ): δ 1.20 (t, J = 7.5 Hz, ethyl-CH ),
3
3
-1 1
–
159 mJ/mg; ir: 2960 m, 1760 s, 1740 m, 1540 s cm ; H nmr
3.40-3.70 (m, 4 CH ), 3.85 (s, NMe), 4.25 (q, J = 7. 5 Hz, ethyl-
2
(
DMSO-d ): δ 3.70 (s, 2 Me), 5.95 (s, CH), 7.90 (t, J = 7.0 Hz, 1
CH ), 4.90 (s, CH), 7.35 (t, J = 7.0 Hz, 1 ArH), 7.45 (d, 7.5 Hz, 1
ArH), 7.70 (t, J = 7.5 Hz, 1 ArH), 8.05 (d, J = 7.5 Hz, 1 ArH); ms:
6
2
1
3
ArH), 8.10 (t, J = 7.1 Hz, 1 ArH), 8.20 (d, J = 7.0 Hz, 2 ArH);
C
nmr (CDCl ): δ = 14.9 (Me), 47.3 (CH), 59.1 (CH ), 124.3 (Ar-
m/z (%) 404 (18, M+1), 403 (100, M), 314 (7).
3
2
CH), 126.2 (Ar-CH), 128.3 (Ar-CH), 128.9 (Ar-CH), 134.5 (Ar-
CH), 140.2 (C-4), 146.6 (C-2), 149.5 (C-8a), 159.1 (ester-C=O).
Anal. Calcd. for C H N O : C, 56.57; H, 5.25; N, 10.42.
19 21 3 7
Found: C, 56.97; H, 5.27; N, 10.03.
Acknowledgment.
Anal. Calcd. for C H ClN O : C, 49.65; H, 3.27; N, 8.27;
1
4
11
2 6
Cl, 10.47. Found: C, 49.77; H, 3.44; N, 8.13, Cl, 10.40.
We would like to thank Dr. Gottfried Faleschini, Institute of
Inorganic Chemistry, Karl Franzens University of Graz, for his
support in the thermogravimetric measurements.
Ethyl 3-(6-Chloropyridin-3-ylmethylamino)-2-(1-methyl-3-
nitro-2-oxo-1,2-dihydroquinolin-4-yl)-3-oxopropanoate (13a).
A solution of quinolinylmalonate 3f (1.81 g, 5 mmol) and 6-
chloro-3-pyridylmethanamine (12a) (1.42 g, 10 mmol) in toluene
REFERENCES AND NOTES
(
30 mL) was heated under reflux for 30 min. After cooling,
hexane (40 mL) was added and the resulting precipitate filtered
by suction. The yield was 2.17 g (78 %), light yellow micro-
prisms, mp 116 °C (toluene/hexane); ir: 3300 m, 1740 m, 1640 s
[1a] A. E. Täubl and W. Stadlbauer, J. Heterocyclic Chem. 34,
989 (1997); [b] W. Stadlbauer, H. Prokopcova, J. Sefcovikova and A.
E. Täubl, Proceedings of ECSOC-7, The Seventh International
Electronic Conference on Synthetic Organic Chemistry 2003; J. A.
Seijas, D.-C. Ji, S.-K. Lin (Eds). CD-ROM edition, ISBN 3-906980-
-1 1
cm ; H nmr (CDCl ): δ 1.03 (t, J = 7.1 Hz, ethyl-CH ), 3.72 (s,
3
3
NMe), 4.12-4.14 (m, ethyl-CH ), 4.39-4.40 (m, N-CH ), 5.10 (s,
2
2
CH), 7.36 (d, J = 7.7 Hz, 1 ArH), 7.48 (t, J = 8.0 Hz, 1 ArH), 7.55
d, J = 8.5 Hz, 1 ArH), 7.71-7.79 (m, 2 ArH), 8.27-8.32 (m, 2
ArH); ms: m/z (%) 460 (25, M+2), 458 (60, M), 370 (43), 368
100), 342 (15), 340 (31), 168 (33), 142 (55), 144 (21).
Anal. Calcd. for C H ClN O : C, 54.97; H, 4.17; N, 12.21.
1
3-8, MDPI, Basel (Switzerland), 2003.
2] V. Dolle, C. H. Nguyen and E. Bisagni, Tetrahedron, 53,
2505 (1997).
3] N. Nishiwaki, A. Tanaka, M. Uchida, Y. Tohda and M.
Ariga, Bull. Chem. Soc. Jap., 69, 1377 (1996).
4] N. Nishiwaki, C. Tanaka, M. Asahara, N. Asaka, Y. Tohda
and M. Ariga, Heterocycles, 51, 567 (1999).
5] D. R. Brittain, E. D. Brown, W. Hepworth and G. J. Stacey
Imperial Chem. Ind. Ltd., UK), Ger. Offen., 76-2611824 (1976);
(
[
1
(
[
2
1
19
4 6
Found: C, 54.81; H, 3.87; N, 12.13.
[
Ethyl 3-[N-(6-Chloropyridin-3-ylmethyl)-N-methylamino]-2-(1-
methyl-3-nitro-2-oxo-1,2-dihydroquinolin-4-yl)-3-oxopro-
panoate (13b).
[
(
Chem. Abstr., 86, 16558 (1977).
This compound was obtained from quinolinylmalonate 3f
1.81 g, 5 mmol) and N-methyl-6-chloro-3-pyridylmethanamine
[6] L. Capuano, V. Diehl and W. Ebner, Chem. Ber., 105, 3407
(1972).
(
(12b) (1.56 g, 10 mmol) according to the method described for
[7] R. M. Titkova, A. S. Elina, E. A. Trifonova, I. V. Persianova,
N. P. Solov'eva, E. M. Peresleni, T. A. Gus'kova and Yu. N. Sheinker,
Khim. Geterotsikl. Soedin., 792 (1981).
1
3a; the yield was 2.43 g (83 %), light yellow prisms, mp 148 °C
-1 1
(ligroin); ir: 2950 w, 1740 s, 1650 s cm ; H nmr (CDCl ): δ
3
[
8] W. Steinschifter and W. Stadlbauer, J. Prakt. Chem. - Chem.
1
4
7
2
.15 (t, J = 7.1 Hz, ethyl-CH ), 3.69 (s, NMe), 3.79 (s, NMe),
2
Ztg., 336, 311 (1994).
.18-4.29 (m, ethyl-CH ), 4.63 (s, N-CH ), 5.00 (s, CH), 7.28-
2
2
[
9] W. Stadlbauer and Th. Kappe, Monatsh. Chem., 113, 751
.33 (m, 2 ArH), 7.45 (d, J = 8.6 Hz, 1 ArH), 7.60 (dd, J = 8.1 and
.1 Hz, 1 ArH), 7.68-7.71 (m, 1 ArH), 7.98 (d, J = 8.2 Hz, 1
(
1982).
[
10] G. M. Coppola and G. E. Hardtmann, J. Heterocyclic
ArH), 8.29 (s, 1 ArH).
Anal. Calcd. for C H ClN O : C, 55.88; H, 4.48; N, 11.85.
Found: C, 56.01; H, 4.31; N 11.50
Chemistry, 16, 1605 (1979).
2
2
21
4
6
[11] P. Roschger and W. Stadlbauer, Liebigs Ann. Chem., 821
(
1990); W. Steinschifter, W. Fiala and W. Stadlbauer, J. Heterocyclic
Chem., 31 1647 (1994).
12] P. Roschger and W. Stadlbauer, J. Heterocyclic Chem., 29,
25 (1992).
[13] A. E. Täubl, K. Langhans, Th. Kappe and W. Stadlbauer, J.
Heterocyclic Chem., 39, 1259 (2002).
Ethyl 2-(1-Methyl-3-nitro-2-oxo-1,2-dihydroquinolin-4-yl)-3-
morpholino-3-oxopropanoat (14).
[
2
This compound was obtained from quinolinylmalonate 3f
1.81 g, 5 mmol) and morpholine (0.87 g, 10 mmol) according to
(