Reductive coupling reactions of 2-nitrochalcones and their β-hydroxy-analogues: New syntheses of 2-arylquinoline and 2-aryl-4-hydroxyquinoline derivatives

Article abstract of DOI:10.1007/s00706-007-0647-9

A one-pot synthesis of novel 2-arylquinolines and 2-aryl-4- hydroxyquinolines was developed from the intramolecular reductive coupling reactions of 2-nitrochalcones and 3-hydroxy-1-phenyl-3-(2-nitrophenyl)-2-propen- 1-ones. Depending on the reduction method and on the presence of electron donating substituents on the A ring of 2-nitrochalcones one can modulate the formation of 2-arylquinolines, their N-oxides, and of 2-aminochalcones. The reduction of 3-hydroxy-1-(2-hydroxyphenyl)-3-(2-nitrophenyl)-2-propen-1-ones with stannous chloride in hydrochloric acid gave 2′-aminoflavones and with ammonium formate and Pd/C yielded 2-(2-hydroxyaryl)-4-hydroxyquinolines. Springer-Verlag 2007.

Full text of DOI:10.1007/s00706-007-0647-9

Monatshefte fu¨r Chemie 138, 585–594 (2007)
DOI 10.1007/s00706-007-0647-9
Printed in The Netherlands
Reductive Coupling Reactions of 2-Nitrochalcones and their b-Hydroxy-
analogues: New Syntheses of 2-Arylquinoline and 2-Aryl-4-hydroxyquinoline
Derivatives
1
1
2;ꢀ
´
Ana I. R. N. A. Barros , Andre F. R. Dias , and Artur M. S. Silva
1
´
Chemistry Department, University of Tras-os-Montes e Alto Douro, Vila Real, Portugal
2
Chemistry Department, University of Aveiro, Aveiro, Portugal
Received November 20, 2006; accepted (revised) December 12, 2006; published online May 10, 2007
# Springer-Verlag 2007
Summary. A one-pot synthesis of novel 2-arylquinolines
their chelation with metal ions; some of these chelates
and 2-aryl-4-hydroxyquinolines was developed from the intra-
molecular reductive coupling reactions of 2-nitrochalcones
and 3-hydroxy-1-phenyl-3-(2-nitrophenyl)-2-propen-1-ones.
Depending on the reduction method and on the presence of
electron donating substituents on the A ring of 2-nitrochal-
cones one can modulate the formation of 2-arylquinolines,
their N-oxides, and of 2-aminochalcones. The reduction of
3-hydroxy-1-(2-hydroxyphenyl)-3-(2-nitrophenyl)-2-propen-
1-ones with stannous chloride in hydrochloric acid gave 20-
aminoflavones and with ammonium formate and Pd=C yielded
2-(2-hydroxyaryl)-4-hydroxyquinolines.
present significant fungicide activity. For instance,
8-hydroxyquinoline derivatives have been extensively
used as a reagent for qualitative and quantitative
determination of several transition metal ions [2].
These important applications and the loss of efficacy
of synthetic drugs based on a quinoline structure
(the alkaloid quinine has been used as a drug in
the treatment of malaria for many centuries), due to
the development of resistant strains of plasmodia,
led the scientific community to pay attention to the
establishment of new methodologies for the synth-
esis of new quinoline derivatives [2, 4]. The struc-
tural core of quinoline has generally been synthesized
by various conventional named reactions, such as
Skraup, Doebner-von Miller, Conrad-Limpach, and
Combes syntheses [1]. These classical methods are
well-known and frequently used for the preparation
of pharmaceutical agents. Due to the interesting and
important biological properties of quinoline deriva-
tives, many other synthesis methods are reported in
the literature for this type of compounds [5], how-
ever the development of new and efficient methods
for the preparation of these important molecules still
continues to be an important and attractive area of
research in synthetic organic chemistry [6, 7].
Keywords. 2-Arylquinolines; 2-Aryl-4-hydroxyquinolines;
Quinolines-N-oxides; 2-Nitrochalcones; Reductive coupling
reactions.
Introduction
The quinoline skeleton occurs naturally, especially
in alkaloids [1], and is often used synthetically to
design compounds with interesting pharmacological
properties (e.g. anesthetics, anxiolytics, antimalarials
and antiseptic agents), or polymers (polyquinolines
and polyvinylquinolines), or cyanine dyes (as sen-
sitizers in photographic emulsions), or antioxidants
in the rubber industry, or fungicides and also as re-
agents in organic synthesis (e.g. in the synthesis of
2-quinolones and 2-octalones) [2–4]. Other important
applications of certain quinoline derivatives involve
In the last decade, the cyclisation of 20-amino-
chalcones has been extensively studied since it pro-
vides 2-aryl-4-quinolone derivatives [5, 8, 9], which
ꢀ
Corresponding author. E-mail: arturs@dq.ua.pt

586
A. I. R. N. A. Barros et al.
present important pharmacological activities [9, 10].
More recently, 20-aminochalcones have been used
in the preparation of 2-aryl-4-chloro-N-formyl-
1,2-dihydroquinolines from their cyclisation under
Vilsmeier conditions [5]. Recently we reported a one-
pot and facile synthesis of 2-(2-hydroxyaryl)quino-
lines from the intramolecular reductive coupling
reaction of 20-hydroxy-2-nitrochalcones [11], where
it was observed that one can modulate the obtained
compounds according to the electron donating or
withdrawing character of the A ring substituents.
So, the reduction of 20-hydroxy-2-nitrochalcones
unsubstituted on the A ring or having 50-bromo
substituents, independently of the used reduction
method (ammonium formate and Pd=C or stannous
chloride in acidic medium) gave a mixture of
2-(2-hydroxyaryl)quinolines and 2-(2-hydroxyaryl)-
quinolines-N-oxides while the reduction of 20-hy-
droxy-2-nitrochalcones bearing electron donating
substituents (40-OCH3 or 40-OBn), gave the correspond-
ing amino-20-hydroxychalcones by using ammonium
formate and Pd=C, and 2-(2-hydroxyaryl)quinolines
by using stannous chloride in acidic medium [11].
Aminochalcones and aminoflavones derivatives are
also interesting pharmacological molecules. Flavones
bearing amino groups on the A or B ring have been
reported to be potential antineoplastic agents [12] and
proved to be antimutagenic in the Ames test using
different species of mutagens [13]. On the other hand
it was found that a series of aminochalcones, synthe-
sized as candidate of cytotoxic agents, displayed se-
lective toxicity to certain malignant cell and were
well tolerated in mice [14].
Following our interest in the reactivity of chalcone
derivatives, reductive coupling reactions using stan-
nous chloride in acidic medium and ammonium
formate and Pd=C were applied to other A-ring
substituted 2-nitrochalcones, 20-hydroxy-3- and -4-
nitrochalcones and 3-hydroxy-1-(2-hydroxyphenyl)-
3-(2-nitrophenyl)-2-propen-1-ones, in order to
compare both methods in terms of the synthesized
products and of the obtained yields.
Results and Discussion
Synthesis
2-Nitrochalcones 1a–1l were obtained from an aldol
condensation of the appropriate acetophenones and
benzaldehydes [15, 16], and 3-hydroxy-1-(2-hydro-
xyphenyl)-3-(2-nitrophenyl)-2-propen-1-ones 5a–5c
were obtained from adequate 20-hydroxyaceto-
phenones and benzoyl chloride derivatives by the
Baker-Venkataraman approach [16]. Taking in ac-
count our study on the reductions of 20-hydroxy-2-
nitrochalcones [11] we decided to apply these reduc-
tion methods to other nitrochalcones and make a com-
parative study in order to get information about the
methodgeneralityin thesynthesis ofthe corresponding
aminochalcones and=or 2-hydroxyarylquinolines.
The treatment of 20-hydroxy-3- or -4-nitrochalcones
1a–1d with ammonium formate and Pd=C, in meth-
Scheme 1

Reductive Coupling Reactions of 2-Nitrochalcones
587
anol at room temperature for 3 h, gave the cor-
responding aminochalcones 2a–2d (Scheme 1).
Under these conditions only occurs the reduction of
the nitro substituents and there was no reduction of
the chalcones double bond. In the case of 50-bromo-
3- and -4-nitrochalcones 1e, 1f there was the reduc-
tion of the nitro group and a debromination process
giving the corresponding 3- and 4-amino-20-hy-
droxychalcones 2a, 2b [17]. Therefore, the amino-
chalcones 2a–2f were obtained by the reduction of
Scheme 2
Scheme 3

588
A. I. R. N. A. Barros et al.
20-hydroxy-3- and -4-nitrochalcones 1a–1f with an
excess of hydrated stannous chloride in hydrochloric
acid (Scheme 1). Although in both cases the amino-
chalcones were obtained in good yields, the reduc-
tion with ammonium formate and Pd=C always gave
better yields (64–83%) than that using stannous chlo-
ride in acidic medium (54–68%) and the work up
was also straightforward.
The treatment of 20-hydroxy-2-nitrochalcones 1g,
1h with an excess of hydrated stannous chloride in
hydrochloric acid gave 2-(2-hydroxyaryl)quinolines
4g, 4h (44–47%) and of 2-(2-hydroxyaryl)quinoline-
N-oxides 3g, 3h (23–27%). However, 20-hydroxy-2-
nitrochalcones 1i–1l gave only the corresponding
2-arylquinolines 4i–4l (49–66%) (Scheme 2). The
treatment of 20-hydroxy-2-nitrochalcones 1g, 1h with
ammonium formate and Pd=C yielded also 2-(2-
hydroxyaryl)quinolines 4g, 4h (37–39%) and of
2-(2-hydroxyaryl)quinoline-N-oxides 3g, 3h (33–
36%); in the case of 40-substituted 2-nitrochalcones
1i, 1j, 1l the corresponding 2-aminochalcones 2i, 2j,
2l (25–68%) were obtained (Scheme 2). These results
indicated that the 20-hydroxy group does not influence
the intramolecular reductive coupling=reduction reac-
tions and support the mechanism that we have previ-
ously proposed [11]. Thus the presence of a electron
donating substituents at C-40 is important to modu-
late the obtained products.
The results obtained in the intramolecular reductive
coupling reactions of 2-nitrochalcones 1g–1l and the
structural similarity with 3-hydroxy-1-(2-hydro-
xyphenyl)-3-(2-nitrophenyl)-2-propen-1-ones 5a–5c,
which can be seen as ꢀ,20-dihydroxy-2-nitrochal-
cones, which are being used as intermediates in the syn-
thesis of 20-nitroflavones by the Baker-Venkataraman
approach [16], let us to study the behaviour of 5a–5c
towards stannous chloride in hydrochloric acid and
to ammonium formate-Pd=C in methanol (Scheme 3).
The treatment of 5a–5c with stannous chloride in
hydrochloric acid led to the formation of 20-amino-
flavones 6a–6c. In a one-pot synthesis we had the
nitro group reduction and a cyclodehydration of
the corresponding diketones catalysed by the acidic
medium [18] leading to the formation of 20-amino-
flavones 6a–6c, which constitutes, to our best know-
ledge, a new synthesis of 20-aminoflavones 6a–6c.
These compounds 6a–6c were obtained in moderate
yields (38–59%).
for 3 h led to the formation of 2-(2-hydroxyaryl)-4-
hydroxyquinolines 8b, 8c (Scheme 3). However,
the treatment of 5a with ammonium formate and
Pd=C in the same conditions, yielded a mixture of
2-(2-hydroxyphenyl)-4-hydroxyquinoline 8a (34%)
and 2-(2-hydroxyphenyl)-4-hydroxyquinoline-N-
oxide 7a (52%). These results confirm and support
our hypothesis that in the absence of electron do-
nating groups in the A ring, the reduction of hy-
droxylamine derivatives is very slow, allowing the
formation of quinoline-N-oxides [11].
NMR Spectroscopy
1
The main H NMR characteristics of the 3- and
4-amino-20-hydroxychalcones 2a–2f are the reso-
nances of the amino group appearing in almost all
cases as a broad singlet at ꢁ 4.05–5.24 ppm and of
the hydroxyl group, which appears as a narrow sing-
let at high frequency values (ꢁ 12.50–13.71 ppm)
due to the existence of an intramolecular hydrogen
bond with the carbonyl oxygen atom. The vinylic
protons of these compounds appear as two doublets
(at ꢁ 7.36–7.84 ppm for H-ꢂ and ꢁ 7.68–7.90 ppm
for H-ꢀ) with a coupling constant typical of a
(E)-configuration (3JHꢂ-Hꢀ 15–16 Hz). From the
13C NMR spectra of 2a–2f one can notice the re-
sonances of C-ꢂ (ꢁ 114.6–120.8 ppm) and C-ꢀ
(ꢁ 144.7–147.0 ppm); being the latter deshielded rel-
atively to the former due to the mesomeric deshield-
ing effect of the carbonyl group. It is also important
to refer the shielding effect of the 4-amino group
on the C-ꢂ carbon resonance (ꢁ 114.6–115.6 ppm)
of 4-aminochalcones 2a, 2c, 2e relatively to those of
3-aminochalcones (ꢁ 119.2–120.8 ppm) due to the
conjugation with the ꢂ,ꢀ-unsaturated system which
increase the electronic density on C-ꢂ. In the 13C NMR
spectra of 2a–2f one can also observe other two
typical carbon resonances, those of C-20 and C¼O
appearing at ꢁ 161.8–166.6 and 191.9–193.6 ppm.
The NMR data of 2-amino-20-hydroxychalcones 2i,
2j, 2l are similar to that of 2a–2f except for the pro-
ton and carbon resonances of the vinylic system, due
to the already reported steric interactions between
H-ꢀ and the 20-substituent, which are responsible
for the deshielding effect of the H-ꢀ (appearing at
ꢁ 7.97–8.05 ppm) and shielding of the corresponding
carbon C-ꢀ (appearing at ꢁ 139.6–139.8 ppm) [19].
The characteristics of the NMR data of 2-(2-hydro-
xyaryl)quinolines 4g–4j which support their struc-
The treatment of 5b and 5c with ammonium for-
mate and Pd=C in methanol at room temperature

Reductive Coupling Reactions of 2-Nitrochalcones
589
ture are the: i) presence of a hydroxyl group involved
in a strong hydrogen bond (ꢁOH 14.93–15.34 ppm in
the 1H NMR spectra); ii) absence of double bonds in
a (E)-configuration, well established in the 1H NMR
spectra of chalcones; iii) absence of carbonyl grouþps
147.2 ppm; v) C-2 at ꢁ 162.2–165.0 ppm; and vi) the
carbonyl group appearing at ꢁ 176.4–177.9 ppm [20].
The confirmation of all proton and carbon reso-
nances and the assignments of those of the quatern-
ary carbons were based on the connectivities found
in the HMBC spectra of all compounds reported in
this report.
in the 13
C NMR spectra; and iv) molecular ions (M ꢁ
in the EIMS) corresponding to the reduction of the
nitro substituent into the amino group and the loss of
one water molecule. From their 1H NMR spectra one
can also notice the typical resonances of H-3 (doub-
Experimental
3
Melting points were measured in a Bu¨chi 535 apparatus. NMR
spectra were recorded on a Bruker Avance 300 spectrometer
(300.13 for 1H and 75.47MHz for 13C), with DMSO-d6 as the
solvent. Chemical shifts (ꢁ) are reported in ppm and coupling
constants (J) in Hz. The internal standard was TMS. Unequi-
vocal 13C assignments were made with the aid of 2D gHSQC
and gHMBC (delays for one bond and long-range J C=H
couplings were optimised for 145 and 7 Hz, respectively) ex-
periments. Electron impact (EI, 70eV) MS were recorded on
VG Autospec Q and M spectrometers [high resolution mass
spectra were in good agreement (ꢃ5 ppm) with the calculat-
ed values]. Elemental Analyses (CHN) were obtained with a
Carlo Erba 1108 CHNS analyzer and were in good agreement
(ꢃ0.4%) with the calculated values. Preparative thin-layer
chromatography was performed with Merck silica gel 60
DGF254. Column chromatography was performed with Merck
silica gel 60, 70–230 mesh. All other chemicals and solvents
used were obtained from commercial sources and used as
received or dried using standard procedures.
let, JH3-H4 ꢂ 9 Hz), H-4 (doublet), and H-8 appear-
ing at ꢁ 8.21–8.46, 8.47–8.61, and 7.96–8.09 ppm,
while from the 13C NMR spectra one can refer the
carbon resonances of C-2 (ꢁ 156.3–158.0 ppm), C-3
(ꢁ 117.5–118.4 ppm), C-4 (ꢁ 138.0–138.6 ppm), and
C-8 (ꢁ 126.5–128.0 ppm). 2-(2-Hydroxyaryl)quino-
line-N-oxides 3g, 3h present similar spectroscopic
features to those of 4g, 4h, but the hydroxyl group
involved in a hydrogen bond appears at lower fre-
quency values (ꢁOH 11.30–11.37ppm in the 1H NMR
þ
spectra) and the molecular ion (M ꢁ in the EIMS)
presents 16 a.m.u. more. One can also notice the im-
portant shielding effect on carbons C-2 (Dꢁ ꢂ 10 ppm)
and C-4 and C-8 (Áꢁ ꢂ 8 ppm) and deshielding ef-
fect on carbon C-3 (Áꢁ ꢂ 6 ppm) of 3g, 3h relatively
to those of 4g, 4h. The NMR data of 2-arylquino-
lines 4k, 4l are similar to that of 4a, 4j except the
absence of the 2-hydroxyl group.
20-Hydroxy-2-nitrochalcones 1a–1j and 3-hydroxy-1-
(2-hydroxyphenyl)-3-(2-nitrophenyl)-2-propen-1-ones 5a–5c
have been prepared according to Refs. [15, 16].
1
As the main H NMR characteristics of 2-(2-hy-
droxyphenyl)-4-hydroxyquinolines 8a–8c one can
notice the proton resonances of the 20-OH and H-3,
appearing as broad singlets at ꢁH 11.24–12.35
and 6.40–6.57 ppm, and also those of H-5 and
H-8 which appear at relatively high frequency
values (ꢁH 8.20–8.44 and 8.20–8.26 ppm). From
the 13C NMR of 8a–8c one can observe the typical
resonances of C-2 (ꢁC 146.4–150.1 ppm), C-3 (ꢁC
102.1–106.5 ppm), C-4 (ꢁC 157.8–164.8 ppm), C-8
(ꢁC 123.2–124.4 ppm), and also C-20 (ꢁC 157.4–
160.3 ppm). 2-(2-Hydroxyaryl)-4-hydroxyquinoline-
N-oxide 7a presents similar spectroscopic features
to those of 8a, but the hydroxyl group involved in
a hydrogen bond appears at lower frequency values
(ꢁOH 12.00 ppm in the 1H NMR spectra) and the mole-
Synthesis of 2-Nitrochalcones 1k and 1l
Sodium hydride (0.88 g, 36.5mmol) was slowly added to a so-
lution of the appropriate acetophenone (16.6mmol) in 10cm3
THF and the reaction mixture stirred at room temperature for
20 minutes. After this period a solution of 2.76g 2-nitro-
benzaldehyde (18.3 mmol) in 10 cm3 THF was added to the
reaction mixture. The solution was stirred under N2 at room
temperature for 2 h. The disappearance of the starting ma-
terials was monitored by tlc. The reaction mixture was poured
into 50 g ice and 50 cm3 H2O, and the pH adjusted to 3
with HCl. The obtained solid was removed by filtration, taken
up in 2ꢄ30cm3 CHCl3 and washed with 2ꢄ20 cm3 H2O.
The organic layer was dried (Na2SO4) and evaporated to
dryness; the obtained crude material was chromatographed
over a silica gel column (eluent: several mixtures of light
petroleum:chloroform to eliminate undesired compounds and,
lastly CHCl3) to provide 1k and 1l. Both compounds were
recrystallised from ethanol.
þ
cular ion (M ꢁin the EIMS) presents 16 a.m.u. more.
The main features of the NMR data of 20-amino-
flavones 6a–6c are the resonances of: i) H-3 ap-
pearing as a singlet at ꢁ 6.36–6.70 ppm; ii) NH2
appearing as a broad singlet at ꢁ 5.61–5.71 ppm;
iii) C-3 at ꢁ 107.4–111.1 ppm; iv) C-20 at ꢁ 146.9–
2-Nitrochalcone (1k, C15H11NO3)
1
Yield 42%, mp: 97–98ꢅC; H NMR (300MHz, DMSO-d6):
ꢁ ¼ 7.33 (d, J ¼ 15.7Hz, H-ꢂ), 7.45–7.52 (m, H-4), 7.53 (d,
J ¼ 7.8Hz, H-30,50), 7.58–7.61 (m, H-40), 7.71 (dt, J ¼ 1.1,
7.1 Hz, H-5), 7.75 (dd, J ¼ 1.7, 7.1 Hz, H-6), 8.02 (d,

590
A. I. R. N. A. Barros et al.
J ¼ 7.8 Hz, H-20,60), 8.08 (dd, J ¼ 1.1, 8.1 Hz, H-3), 8.14 (d,
J ¼ 15.7Hz, H-ꢀ) ppm; 13C NMR (75 MHz, DMSO-d6):
ꢁ ¼ 125.0 (C-3), 127.3 (C-ꢂ), 128.7 (C-30,50), 128.8 (C-20,60),
129.2 (C-6), 130.3 (C-4), 131.3 (C-1), 133.2 (C-40), 133.8
(C-5), 137.3 (C-10), 140.2 (C-ꢀ), 148.9 (C-2), 190.5 (C¼O)
ppm; IR (KBr): ꢃꢀ¼ 1681, 1670, 1569, 1513, 1340, 1214,
1012, 858, 740, 684 cmꢆ1; MS (EI, 70 eV): m=z (%) ¼ 253
on charcoal in 10 cm3 dry methanol at room temperature,
wasaddedanhydrousammoniumformate(23 mmol), inasingle
portion under N2. The resulting mixture was stirred at room
temperature for 3 h. The catalyst was removed by filtration
through celite and washed with 2ꢄ10 cm3 methanol. The
filtrate was evaporated under reduced pressure and the resi-
due was taken up in CHCl3 and washed with 3ꢄ25 cm3
H2O. The organic layer was dried (Na2SO4) and evaporated
to dryness.
In the case of 20-hydroxy-3- and 4-nitrochalcones 1a–1d,
the obtained residue was recrystallized from ethanol, giving
the corresponding 3- and 4-amino-20-hydroxychalcones
2a–2d (2a, 77%; 2b, 83%; 2c, 72%; 2d, 68%). For 50-
bromo-3- and -4-nitrochalcones 1e, 1f, there was the forma-
tion of 3- and 4-amino-20-hydroxychalcone 2a, 2b (2a, 64%;
2b, 68%). For 40-substituted-20-hydroxy-2-nitrochalcones 1i,
1j, the obtained residue was recrystallized from ethanol, giving
also the correspondent amino derivatives, 2-amino-20-hydro-
xychalcones 2i, 2j (2i, 68%; 2j, 50%). For 40-methoxy-2-nitro-
chalcone 1l the obtained crude material was chromatographed
over a silica gel column (eluent, chloroform) to provide
2-amino-40-methoxychalcone 2l (25%).
þ
(M ꢁ, 100), 220 (59), 193 (25), 180 (15), 167 (30), 154 (7).
40-Methoxy-2-nitrochalcone (1l, C16H13NO3)
1
Yield 32%, mp: 93–94ꢅC; H NMR (300 MHz, DMSO-d6):
ꢁ ¼ 3.90 (s, OCH3), 6.99 (d, J ¼ 9.0Hz, H-30,50), 7.33 (d, J ¼
15.6Hz, H-ꢂ), 7.56 (dt, J ¼ 1.7, 7.4 Hz, H-4), 7.68 (dt, J ¼ 1.4,
7.4 Hz, H-5), 7.74 (dd, J ¼ 1.7, 7.4 Hz, H-6), 8.04 (d,
J ¼ 9.0 Hz, H-20,60), 8.06 (dd, J ¼ 1.4, 7.4 Hz, H-3), 8.11 (d,
J ¼ 15.6Hz, H-ꢀ) ppm; 13C NMR (75 MHz, DMSO-d6):
ꢁ ¼ 55.6 (OCH3), 114.0 (C-30,50), 125.0 (C-3), 127.3 (C-ꢂ),
129.3 (C-6), 130.2 (C-4), 130.3 (C-10), 131.2 (C-20,60), 131.5
(C-1), 133.5 (C-5), 139.2 (C-ꢀ), 148.6 (C-2), 163.7 (C-40),
188.7 (C¼O) ppm; IR (KBr): ꢃꢀ¼ 1652, 1602, 1569, 1517,
1421, 1351, 1297, 1259, 1220, 1016, 977, 835, 755 cmꢆ1
.
In the case of 20-hydroxy-2-nitrochalcones 1g, 1h and
3-hydroxy-1-(2-hydroxyphenyl)-3-(2-nitrophenyl)-2-propen-1-
ones 5a–5c, the obtained crude material was chromato-
graphed over a silica gel column (eluent: 1:1 mixture of light
petroleum:chloroform and then chloroform) to provide 2-(2-
hydroxyaryl)quinolines 4g, 4h and also 2-(2-hydroxyaryl)qui-
noline-N-oxides 3g, 3h (3g, 36%; 4g, 39%; 3h, 33%; 4h, 37%)
in the first case, and of 2-(2-hydroxyphenyl)-4-hydroxyquino-
line 8a–8c and the corresponding 2-(2-hydroxyphenyl)-4-
hydroxyquinoline-N-oxide 7a (8a, 52%; 7a, 34%; 8b, 36%;
8c, 63%) for the last one.
General Procedure for the Reduction=Reductive Coupling
With SnCl2 ꢁ 2H2O in HCl=AcOH
A solution of 5.2 g SnCl2 ꢁ 2H2O (23 mmol) in 20cm3 con-
centrated HCl was added to a suspension of the appropriate
2-nitrochalcones 1a–1l or 3-hydroxy-1-(2-hydroxyphenyl)-3-
(2-nitrophenyl)-2-propen-1-ones 5a–5c (5.7mmol), in 60cm3
acetic acid. The obtained mixture was heated at 90ꢅC for 4 h.
After that period, the reaction mixture was cooled and treated
with a 25% aqueous NaOH solution to adjust pH to 9. The
obtained residue was extracted with 2ꢄ50 cm3 CHCl3, dried
(Na2SO4), and evaporated to dryness.
In the case of 20-hydroxy-3- and 4-nitrochalcones 1a–1f,
the obtained residue was recrystallized from ethanol giving
the corresponding 3- and 4-amino-20-hydroxychalcones 2a–2f
(2a, 61%; 2b, 64%; 2c, 54%; 2d, 58%; 2e, 68%; 2f, 54%). For
3-hydroxy-1-(2-hydroxyphenyl)-3-(2-nitrophenyl)2-propen-1-
ones 5a–5c, the obtained residue was recrystallized from
ethanol giving the corresponding 20-aminoflavones 6a–6c
(6a, 38%; 6b, 54%; 6c, 59%).
In the case of 2-nitrochalcones 1i–1l the residue was pur-
ified by silica gel column chromatography, using chloroform
as eluent. After solvent evaporation, the obtained residue was
recrystallized from ethanol to give 2-(2-hydroxyaryl)quino-
lines 4i–4l (4i, 66%; 4j, 58%; 4k, 54%; 4l, 49%). For
20-hydroxy-2-nitrochalcones 1g, 1h the obtained crude mate-
rial was chromatographed over a silica gel column (eluent: 1:1
mixture of light petroleum:chloroform and then chloroform)
to provide 2-(2-hydroxyaryl)quinolines 4g, 4h and the corre-
sponding 2-(2-hydroxyaryl)quinoline-N-oxides 3g, 3h (4g,
47%; 4h, 44%; 3g, 23%; 3h, 27%).
3-Amino-20-hydroxychalcone (2a, C15H13NO2)
Mp: 120–121ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 5.24 (s
br, NH2), 6.70 (d, J ¼ 8.1 Hz, H-30), 6.98 (t, J ¼ 7.4 Hz, H-50),
7.00 (d, J ¼ 7.5 Hz, H-4), 7.01 (s br, H-2), 7.06 (d, J ¼ 7.5 Hz,
H-6), 7.13 (t, J ¼ 7.5Hz, H-5), 7.54 (ddd, J ¼ 1.2, 7.4, 8.1Hz,
H-40), 7.68 (d, J ¼ 15.5Hz, H-ꢀ), 7.84 (d, J ¼ 15.5Hz, H-ꢂ)
8.16 (dd, J ¼ 1.2, 7.4Hz, H-60), 12.50 (s, OH) ppm; 13C NMR
(75 MHz, DMSO-d6): ꢁ ¼ 114.0 (C-2), 117.0 (C-30 and C-6),
117.8 (C-4), 119.2 (C-50), 120.8 (C-ꢂ), 121.0 (C-10), 129.5
(C-5), 130.7 (C-60), 134.9 (C-1), 136.2 (C-40), 146.0 (C-ꢀ),
149.2 (C-3), 161.8 (C-20), 193.6 (C¼O) ppm; IR (KBr):
ꢃꢀ¼ 1641, 1579, 1486, 1440, 1342, 1295, 1203, 1025,
846 cmꢆ1
þ
; MS (EI, 70 eV): m=z (%) ¼ 239 (M ꢁ, 100), 221
(23), 210 (15), 194 (11), 165 (8), 147 (38), 119 (43), 106 (9),
93 (22), 65 (27).
4-Amino-20-hydroxychalcone (2b, C15H13NO2)
1
Mp: 155–157ꢅC; H NMR (300 MHz, DMSO-d6): ꢁ ¼ 4.07
(s br, NH2), 6.70 (d, J ¼ 8.6 Hz, H-3,5), 6.93 (dt, J ¼ 1.1,
8.3 Hz, H-30), 7.02 (dt, J ¼ 1.1, 8.3 Hz, H-50), 7.47 (dt,
J ¼ 1.7, 8.3 Hz, H-40), 7.49 (d, J ¼ 15.4 Hz, H-ꢂ), 7.52
(d, J ¼ 8.6 Hz, H-2,6), 7.89 (d, J ¼ 15.4 Hz, H-ꢀ), 7.94
(dd, J ¼ 1.7, 8.3 Hz, H-60), 13.09 (s, OH) ppm; 13C NMR
(75 MHz, DMSO-d6): ꢁ ¼ 114.8 (C-3,5), 115.5 (C-ꢂ), 118.5
(C-30), 118.6 (C-50), 120.2 (C-10), 124.8 (C-1), 129.4 (C-60),
General Procedure for the Reduction=Reductive Coupling
With Ammonium Formate and Pd=C
To a stirred suspension of the appropriate 2-nitrochalcones
1a–1l or 3-hydroxy-1-(2-hydroxyphenyl)-3-(2-nitrophenyl)-
2-propen-1-ones 5a–5c (5mmol) and 0.25 g 10% palladium

Reductive Coupling Reactions of 2-Nitrochalcones
591
130.9 (C-2,6), 135.9 (C-40), 146.1 (C-ꢀ), 152.7 (C-4), 163.5 (C-
20), 193.6 (C¼O) ppm; IR (KBr): ꢃꢀ¼ 1627, 1546, 1486, 1442,
1302, 1201, 1027, 765 cmꢆ1; MS (EI, 70 eV): m=z (%) ¼ 239
J ¼ 2.4, 8.7 Hz, H-40), 7.90 (d, J ¼ 15.2 Hz, H-ꢀ), 7.99 (d,
J ¼ 2.4 Hz, H-60), 13.04 (s, OH) ppm; 13C NMR (75 MHz,
DMSO-d6): ꢁ ¼ 110.2 (C-50), 114.6 (C-ꢂ), 114.8 (C-3,5),
120.5 (C-30), 124.5 (C-10), 129.4 (C-1), 131.2 (C-2,6),
131.6 (C-60), 138.3 (C-40), 147.3 (C-ꢀ), 149.9 (C-4),
162.4 (C-20), 192.5 (C¼O) ppm; IR (KBr): ꢃꢀ¼ 16313,
1600, 1556, 1515, 1467, 1422, 1336, 1271, þ1172, 1027,
; MS (EI, 70 eV): m=z (%) ¼ 319 (M ꢁ
þ
(M ꢁ, 64), 238 (34), 222 (9), 165 (5), 146 (16), 119 (100), 106
(47), 93 (27), 65 (26).
3-Amino-20-hydroxy-40-methoxychalcone (2c, C16H15NO3)
Mp: 114–115ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 3.85 (s,
OCH3), 6.47 (s br, H-30), 6.50 (dd, J ¼ 2.5, 8.2 Hz, H-50), 6.74
(dt, J ¼ 2.0, 7.8Hz, H-4), 6.93 (t, J ¼ 2.0 Hz, H-2), 7.05 (d,
J ¼ 7.8 Hz H-6), 7.21 (t, J ¼ 7.8Hz, H-5), 7.51 (d, J ¼ 15.4 Hz,
H-ꢂ), 7.79 (d, J ¼ 15.4Hz, H-ꢀ), 7.82 (d, J ¼ 8.2 Hz, H-60),
13.48 (s, OH) ppm; 13C NMR (75 MHz, DMSO-d6): ꢁ ¼ 55.6
(OCH3), 101.0 (C-30), 107.7 (C-50), 114.0 (C-10), 114.5 (C-2),
117.5 (C-4), 119.0 (C-6), 120.0 (C-ꢂ), 129.8 (C-5), 131.2
(C-60), 135.7 (C-1), 144.7 (C-ꢀ), 146.8 (C-3), 166.1 (C-40),
166.6 (C-20), 193.6 (C¼O) ppm; IR (KBr): ꢃꢀ¼ 1637, 1579,
1506, 1359, 1267, 1214, 1128, 1018, 825 cmꢆ1; MS (EI,
823 cmꢆþ1
81Br, 97),
79Br, 100), 300 (7), 238 (16), 209 (9), 180 (7),
317 (M ꢁ
165 (8), 146 (34).
2-Amino-20-hydroxy-40-methoxychalcone (2i, C16H15NO3)
Mp: 157–158ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 3.86 (s,
OCH3), 4.09 (s br, NH2), 6.47 (s br, H-30), 6.50 (dd, J ¼ 2.5,
9.6 Hz, H-50), 6.74 (d, J ¼ 7.6 Hz, H-3), 6.81 (t, J ¼ 7.6 Hz,
H-5), 7.22 (dt, J ¼ 1.2, 7.6 Hz, H-4), 7.50 (d, J ¼ 7.6 Hz, H-6),
7.51 (d, J ¼ 15.2Hz, H-ꢂ), 7.82 (d, J ¼ 9.6 Hz, H-60), 8.05 (d,
J ¼ 15.2 Hz, H-ꢀ), 13.52 (s, OH) ppm; 13C NMR (75 MHz,
DMSO-d6): ꢁ ¼ 55.6 (OCH3), 101.0 (C-30), 107.7 (C-50), 114.1
(C-10), 116.9 (C-3), 118.9 (C-5), 120.1 (C-ꢂ), 120.2 (C-1),
128.2 (C-6), 131.2 (C-60), 131.8 (C-4), 139.7 (C-ꢀ), 146.3
(C-2), 166.1 (C-40), 166.7 (C-20), 191.8 (C¼O) ppm; IR
(KBr): ꢃꢀ¼ 1629, 1577, 1367, 1288 cmꢆ1; MS (EI, 70 eV):
þ
70eV): m=z (%) ¼ 269 (M ꢁ, 100), 268 (48), 252 (15), 252
(15), 240 (6), 177 (47), 151 (48), 146 (6), 119 (35), 108 (12),
91 (15).
4-Amino-20-hydroxy-40-methoxychalcone (2d, C16H15NO3)
Mp: 130–131ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 3.84 (s,
OCH3), 4.05 (s br, NH2), 6.46 (d, J ¼ 2.5 Hz, H-30), 6.47 (dd,
J ¼ 2.5, 6.9 Hz, H-50), 6.68 (d, J ¼ 8.5 Hz, H-3,5), 7.39 (d,
J ¼ 15.5Hz, H-ꢂ), 7.48 (d, J ¼ 8.5 Hz, H-2,6), 7.83 (d, J ¼
15.5Hz, H-ꢀ), 7.85 (d, J ¼ 6.9 Hz, H-60), 13.71 (s, OH) ppm;
13C NMR (75 MHz, DMSO-d6): ꢁ ¼ 55.5 (OCH3), 101.0 (C-
30), 107.4 (C-50), 114.2 (C-10), 114.8 (C-3,5), 115.6 (C-ꢂ),
124.9 (C-1), 130.7 (C-2,6), 131.0 (C-60), 145.0 (C-ꢀ), 149.3
(C-4), 165.8 (C-40), 166.5 (C-20), 191.9 (C¼O) ppm; IR
þ
m=z (%) ¼ 269 (M ꢁ, 27), 252 (62), 251 (100), 250 (38),
222 (8), 208 (11), 180 (10), 151 (33), 146 (16), 128 (15),
118 (34), 108 (12), 91 (17).
2-Amino-40-benzyloxy-20-hydroxychalcone (2j, C22H19NO3)
Mp: 150–151ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 4.09 (s
br, NH2), 5.11 (s, CH2), 6.53–6.57 (m, H-30 and H-50), 6.73
(dd, J ¼ 0.9, 7.9 Hz, H-3), 6.80 (t, J ¼ 7.9 Hz, H-5), 7.21 (dt,
J ¼ 1.4, 7.9 Hz, H-4), 7.34–7.44 (m, H-200,300,400,500,600), 7.49
(d, J ¼ 7.9 Hz, H-6), 7.50 (d, J ¼ 15.2 Hz, H-ꢂ), 7.82 (d,
J ¼ 9.7Hz, H-60), 8.04 (d, J ¼ 15.2Hz, H-ꢀ), 13.49 (s, OH)
ppm; 13C NMR (75 MHz, DMSO-d6): ꢁ ¼ 70.2 (CH2), 102.1
(C-30), 108.2 (C-50), 114.2 (C-10), 116.8 (C-3), 118.9 (C-5),
120.1 (C-ꢂ), 120.2 (C-1), 127.6 (C-200,600), 128.2 (C-400), 128.3
(C-6), 128.7 (C-300,500), 131.2 (C-60), 131.8 (C-4), 135.8 (C-
100), 139.8 (C-ꢀ), 146.3 (C-2), 165.2 (C-40), 166.6 (C-20),
(KBr): ꢃꢀ¼ 1629, 1563, 1508, 1367, 1290, 1226, 1020,
þ
831 cmꢆ1
; MS (EI, 70 eV): m=z (%) ¼ 269 (M ꢁ, 67), 268
(22), 252 (4), 177 (7), 151 (20), 146 (9), 119 (100), 106 (70),
93 (13), 65 (9).
3-Amino-50-bromo-20-hydroxychalcone (2e, C15H12NO2Br)
1
Mp: 1120–121ꢅC; H NMR (300 MHz, DMSO-d6): ꢁ ¼ 6.78
(dt, J ¼ 1.8, 7.8 Hz, H-4), 6.94 (d, J ¼ 8.9 Hz, H-30), 6.98
(t, J ¼ 1.8 Hz, H-2), 7.09 (d, J ¼ 7.8 Hz, H-6), 7.23 (t,
J ¼ 7.8 Hz, H-5), 7.51 (d, J ¼ 15.4Hz, H-ꢂ), 7.57 (dd, J ¼
2.4, 8.9 Hz, H-40), 7.86 (d, J ¼ 15.4 Hz, H-ꢀ), 8.00 (d,
J ¼ 2.4 Hz, H-60), 12.78 (s, OH) ppm; 13C NMR (75 MHz,
DMSO-d6): ꢁ ¼ 110.4 (C-50), 114.5 (C-2), 118.1 (C-4),
119.2 (C-ꢂ), 119.6 (C-6), 120.6 (C-30), 121.3 (C-10),
130.0 (C-5), 130.9 (C-1), 131.8 (C-60), 135.3 (C-3), 138.9
(C-40), 147.0 (C-ꢀ), 162.5 (C-20), 192.8 (C¼O) ppm; IR
(KBr): ꢃꢀ¼ 1643, 1619, 1571, 1463, 1400, 1357, 1332,
191.8 (C¼O) ppm; IR (KBr): ꢃꢀ¼ 1625, 1571, 1359,
þ
1282cmꢆ1
; MS (EI, 70 eV): m=z (%) ¼ 345 (M ꢁ, 15), 327
(52), 299 (3), 237 (8), 208 (13), 180 (7), 146 (5), 118 (12), 91
(100), 65 (14).
2-Amino-40-methoxychalcone (2l, C16H15NO2)
1
Mp: 93–94ꢅC; H NMR (300MHz, DMSO-d6): ꢁ ¼ 3.86 (s,
OCH3), 5.70 (s br, NH2), 6.58 (t, J ¼ 7.8 Hz, H-5), 6.71 (d,
J ¼ 7.8Hz, H-3), 7.08 (d, J ¼ 8.8 Hz, H-30,50), 7.09–7.13 (m,
H-4), 7.81 (d, J ¼ 15.1Hz, H-ꢂ), 7.71 (d, J ¼ 7.8 Hz, H-6),
7.97 (d, J ¼ 15.1 Hz, H-ꢀ), 8.14 (d, J ¼ 8.8 Hz, H-H-20,60)
ppm; 13C NMR (75 MHz, DMSO-d6): ꢁ ¼ 55.6 (OCH3),
114.0 (C-30,50), 114.3 (C-10), 116.3 (C-3), 116.5 (C-5), 118.3
(C-1), 119.4 (C-ꢂ), 127.8 (C-6), 130.7 (C-20,60), 131.5 (C-4),
139.6 (C-ꢀ), 149.0 (C-2), 162.9 (C-40), 187.4 (C¼O) ppm;
IR (KBr): ꢃꢀ¼ 1652, 1604, 1583, 1459, 1336, 1259, 1216,
1110, 1018, 590 cmꢆ1; MS (EI, 70 eV): m=z (%) ¼ 253
1284, 1251, 1176, 844 cmꢆ1; MS (EI, 70 eV): m=z (%) ¼
81
79Br, 100), 301 (73), 290
þ
þ
319 (M ꢁ Br, 100), 317 (M ꢁ
(4), 284 (7), 179 (18), 238 (12), 225 (28), 209 (17), 193
(16), 180 (10), 167 (25), 149 (46).
4-Amino-50-bromo-20-hydroxychalcone (2f, C15H12NO2Br)
1
Mp: 156–158ꢅC; H NMR (300 MHz, DMSO-d6): ꢁ ¼ 6.70
þ
(d, J ¼ 8.5 Hz, H-3,5), 6.92 (d, J ¼ 8.7 Hz, H-30), 7.36 (d,
J ¼ 15.2 Hz, H-ꢂ), 7.52 (d, J ¼ 8.5 Hz, H-2,6), 7.53 (dd,
(M ꢁ, 23), 236 (100), 220 (6), 165 (3), 146 (38), 118 (51),
92 (28), 77 (32), 64 (15).

592
A. I. R. N. A. Barros et al.
þ
(%) ¼ 301 (M ꢁ, 100), 300 (55), 299 (100), 298 (39), 271
(4), 219 (6), 191 (48), 165 (13), 128 (15), 110 (8), 96 (27),
77 (7), 63 (8), 57 (5).
2-(2-Hydroxyphenyl)quinoline-N-oxide (3g, C15H11NO2)
1
Mp: 180–181ꢅC; H NMR (300 MHz, DMSO-d6): ꢁ ¼ 7.05
(dd, J ¼ 1.0, 7.7Hz, H-30), 7.10 (dt, J ¼ 1.0, 7.7 Hz, H-50),
7.53 (dt, J ¼ 1.6, 7.7 Hz, H-40), 7.69 (dd, J ¼ 1.6, 7.7 Hz,
H-60), 7.87 (dt, J ¼ 1.0, 7.8 Hz, H-6), 7.96 (d, J ¼ 8.9 Hz,
H-3), 8.01–8.04 (m, H-7), 8.25 (d, J ¼ 7.8 Hz, H-5), 8.35 (d,
J ¼ 8.9 Hz, H-4), 8.75 (d, J ¼ 8.7 Hz, H-8), 11.30 (s, OH)
ppm; 13C NMR (75 MHz, DMSO-d6): ꢁ ¼ 119.0 (C-8), 119.6
(C-30), 120.0 (C-50), 121.4 (C-10), 124.7 (C-3), 128.7 (C-5),
128.8 (C-4a), 129.2 (C-6), 130.2 (C-4), 132.1 (C-60), 132.2
(C-7), 132.4 (C-40), 139.9 (C-8a), 147.6 (C-2), 159.1 (C-20)
ppm; IR (KBr): ꢃꢀ¼ 1562, 1506, 1481, 1334 cmꢆ1; MS (EI,
2-(2-Hydroxy-4-methoxyphenyl)quinoline (4i, C16H13NO2)
Mp: 123–124ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 3.81 (s,
OCH3), 6.52 (d, J ¼ 2.5Hz, H-30), 6.56 (dd, J ¼ 2.5, 8.8Hz,
H-50), 7.60 (dt, J ¼ 1.0, 7.6 Hz, H-6), 7.80 (dt, J ¼ 1.4, 7.6Hz,
H-7), 7.98–8.01 (m, H-5 and H-8), 8.12 (d, J ¼ 8.8 Hz, H-60),
8.27 (d, J ¼ 9.0 Hz, H-3), 8.50 (d, J ¼ 9.0 Hz, H-4), 15.34 (s,
OH) ppm; 13C NMR (75 MHz, DMSO-d6): ꢁ ¼ 55.5 (OCH3),
101.9 (C-30), 106.4 (C-50), 111.9 (C-10), 117.7 (C-3),
126.0 (C-4a), 126.5 (C-6), 128.0 (C-5 and C-8), 129.1
(C-60), 130.9 (C-7), 138.2 (C-4), 148.9 (C-8a), 157.7 (C-2),
þ
70eV): m=z (%) ¼ 237 (M ꢁ, 48), 221 (32), 220 (100), 208
(7), 191 (20), 180 (15), 165 (14), 140 (5), 128 (9), 102 (3), 95
(6), 77 (5), 63 (4).
162.4 (C-40), 162.6 (C-20) ppm; IR (KBr): ꢃꢀ¼ 1606, 1587,
1548, 1506cmꢆ1
þ
; MS (EI, 70 eV): m=z (%) ¼ 251 (M ꢁ,
100), 250 (42), 222 (19), 208 (34), 180 (32), 167 (7), 154
(13), 128 (22), 112 (8), 77 (12), 63 (6).
2-(5-Bromo-2-hydroxyphenyl)quinoline-N-oxide
(3h, C15H10NO2Br)
1
Mp: 167–168ꢅC; H NMR (300MHz, DMSO-d6): ꢁ ¼ 7.00
(d, J ¼ 8.8 Hz, H-30), 7.65 (dd, J ¼ 2.5, 8.8 Hz, H-40), 7.84 (d,
J ¼ 2.5 Hz, H-60), 7.88 (dt, J ¼ 0.9, 8.0 Hz, H-6), 7.98 (d,
J ¼ 8.8 Hz, H-3), 7.97–8.03 (m, H-7), 8.24 (dd, J ¼ 0.9,
8.0 Hz, H-5), 8.33 (d, J ¼ 8.8 Hz, H-4), 8.72 (d, J ¼ 8.8 Hz,
H-8), 11.37 (s, OH) ppm; 13C NMR (75 MHz, DMSO-d6):
ꢁ ¼ 110.7 (C-50), 119.0 (C-8), 121.4 (C-30), 123.3 (C-10),
124.7 (C-3), 128.7 (C-5), 129.1 (C-4a), 129.3 (C-6), 129.9
(C-4), 131.6 (C-7), 133.8 (C-60), 134.7 (C-40), 139.9 (C-8a),
2-(2,4-Dihydroxyphenyl)quinoline (4j, C15H11NO2)
Mp: 175–176ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 6.36 (d,
J ¼ 2.4Hz, H-30), 6.43 (dd, J ¼ 2.4, 8.7Hz, H-50), 7.59 (dt,
J ¼ 0.9, 8.0 Hz, H-6), 7.76–7.82 (m, H-7), 7.96 (d, J ¼ 8.0 Hz,
H-8), 7.99 (d, J ¼ 8.0Hz, H-5), 8.02 (d, J ¼ 8.7 Hz, H-60),
8.21 (d, J ¼ 9.0 Hz, H-3), 8.47 (d, J ¼ 9.0 Hz, H-4), 10.03 (s,
40-OH), 15.23 (s, 20-OH) ppm; 13C NMR (75 MHz, DMSO-d6):
ꢁ ¼ 103.5 (C-30), 107.5 (C-50), 110.8 (C-10), 117.5 (C-3),
125.8 (C-4a), 126.3 (C-6), 126.5 (C-8), 128.0 (C-5), 129.2
(C-60), 130.8 (C-7), 138.0 (C-4), 144.0 (C-8a), 158.0 (C-2),
145.8 (C-2), 158.2 (C-20) ppm; IR (KBr): ꢃꢀ¼ 1560, 1506,
þ
1473, 1330 cmꢆ1
; MS (EI, 70 eV): m=z (%) ¼ 317 (M ꢁ, 62),
161.2 (C-40), 162.4 (C-20) ppm; IR (KBr): ꢃꢀ¼ 1612, 1582,
315 (62), 300 (100), 286 (7), 219 (66), 208 (8), 191 (43),
180 (23), 164 (13), 140 (7), 128 (27), 96 (22), 77 (12), 63 (14).
1552, 1509cmꢆ1
þ
; MS (EI, 70 eV): m=z (%) ¼ 237 (M ꢁ,
92), 236 (64), 207 (33), 191 (3), 180 (36), 167 (9), 128
(12), 105 (100), 89 (11), 77 (67), 63 (15).
2-(2-Hydroxyphenyl)quinoline (4g, C15H11NO)
1
Mp: 110–111ꢅC; H NMR (300 MHz, DMSO-d6): ꢁ ¼ 6.97–
7.03 (m, H-30 and H-50), 7.41 (dt, J ¼ 1.2, 7.7Hz, H-40), 7.67
(dt, J ¼ 0.7, 7.5 Hz, H-6), 7.85 (dt, J ¼ 1.1, 7.5 Hz, H-7), 8.05–
8.10 (m, H-5 and H-8), 8.22 (dd, J ¼ 1.2, 7.7Hz, H-60), 8.39
(d, J ¼ 8.9 Hz, H-3), 8.59 (d, J ¼ 8.9Hz, H-4), 14.93 (s, OH)
ppm; 13C NMR (75 MHz, DMSO-d6): ꢁ ¼ 118.0 (C-3 and
C-30), 118.8 (C-10), 118.9 (C-50), 126.4 (C-4a), 127.0 (C-6 and
C-8), 127.9 (C-60), 128.0 (C-5), 130.9 (C-7), 132.2 (C-40),
138.4 (C-4), 144.1 (C-8a), 157.7 (C-2), 160.2 (C-20) ppm;
IR (KBr): ꢃꢀ¼ 1606, 1585, 1550, 1506cmꢆ1; MS (EI,
2-Phenylquinoline (4k, C15H11NO2)
1
Mp: 66–68ꢅC; H NMR (300MHz, DMSO-d6): ꢁ ¼ 7.48 (d,
J ¼ 7.0Hz, H-40), 7.52 (d, J ¼ 7.0 Hz, H-20,60), 7.53–7.56 (m,
H-6), 7.73 (dt, J ¼ 1.4, 7.7 Hz, H-7), 7.84 (dd, J ¼ 1.4, 8.7 Hz,
H-5), 7.88 (d, J ¼ 8.7 Hz, H-3), 8.16 (d, J ¼ 7.0 Hz, H-30,50),
8.18 (d, J ¼ 7.7 Hz, H-8), 8.23 (d, J ¼ 8.7 Hz, H-4) ppm; 13C
NMR (75 MHz, DMSO-d6): ꢁ ¼ 119.0 (C-3), 126.3 (C-6),
127.2 (C-4a), 127.4 (C-5), 127.6 (C-20,60), 128.8 (C-30,50),
129.3 (C-40), 129.6 (C-8), 129.7 (C-7), 136.8 (C-4), 139.6
(C-10), 148.2 (C-8a), 157.3 (C-2) ppm; IR (KBr): ꢃꢀ¼ 1727,
1596, 1490, 1282, 1126, 1072, 829, 771, 690 cmꢆ1; MS (EI,
þ
70eV): m=z (%) ¼ 221 (M ꢁ, 100), 220 (59), 193 (25), 180
(15), 167 (30), 154 (7), 128 (16), 111 (8), 96 (10), 89 (4), 84
(15), 77 (9), 63 (7).
þ
70eV): m=z (%) ¼ 205 (M ꢁ, 100), 204 (72), 176 (6), 167
(14), 149 (35), 102 (16), 71 (12), 57 (19).
2-(5-Bromo-2-hydroxyphenyl)quinoline (4h, C15H10NOBr)
Mp: 165–166ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 6.99 (d,
J ¼ 8.7 Hz, H-30), 7.54 (dd, J ¼ 2.2, 8.7 Hz, H-40), 7.69 (t,
J ¼ 7.4 Hz, H-6), 7.86 (t, J ¼ 7.4 Hz, H-7), 8.07–8.11 (m,
H-5 and H-8), 8.39 (d, J ¼ 2.2 Hz, H-60), 8.46 (d, J ¼ 8.9 Hz,
H-3), 8.61 (d, J ¼ 8.9 Hz, H-4), 14.94 (s, OH) ppm; 13C NMR
(75 MHz, DMSO-d6): ꢁ ¼ 110.1 (C-50), 118.4 (C-3), 120.3
(C-30), 120.9 (C-10), 126.7 (C-4a), 127.2 (C-8), 127.4 (C-6),
128.0 (C-5), 130.1 (C-60), 131.1 (C-7), 134.5 (C-40), 138.6
(C-4), 144.0 (C-8a), 156.3 (C-2), 159.2 (C-20) ppm; IR (KBr):
ꢃꢀ¼ 1604, 1579, 1550, 1509 cmꢆ1; MS (EI, 70 eV): m=z
2-(4-Methoxyphenyl)quinoline (4l, C16H13NO)
1
Mp: 87–89ꢅC; H NMR (300MHz, DMSO-d6): ꢁ ¼ 3.85 (s,
OCH3), 7.11 (d, J ¼ 8.6H, H-30,50), 7.67 (t, J ¼ 7.7 Hz, H-6),
7.77 (t, J ¼ 7.7Hz, H-7), 7.87 (d, J ¼ 7.7 Hz, H-5), 8.04 (d,
J ¼ 7.7Hz, H-8), 8.10 (d, J ¼ 8.6 Hz, H-3), 8.26 (d, J ¼ 8.6 Hz,
H-20,60), 8.41 (d, H-4, J ¼ 8.6 Hz) ppm; 13C NMR (75 MHz,
DMSO-d6): ꢁ ¼ 55.4 (OCH3), 114.3 (C-30,50), 118.4 (C-3),
126.1 (C-6), 127.5 (C-4a), 127.8 (C-5), 128.7 (C-20,60),
129.0 (C-8), 129.9 (C-7), 136.4 (C-10), 137.1 (C-4), 147.6
(C-8a), 155.8 (C-2), 160.7 (C-40) ppm; IR (KBr): ꢃꢀ¼ 1743,

Reductive Coupling Reactions of 2-Nitrochalcones
593
1576, 1493, 1280, 1136, 834, 779, 699 cmꢆ1; MS (EI, 70 eV):
(t, J ¼ 8.0 Hz, H-7), 8.24 (d, J ¼ 8.0 Hz, H-8), 8.27 (d,
J ¼ 8.0 Hz, H-5), 12.29 (br s, OH) ppm; 13C NMR (75 MHz,
DMSO-d6): ꢁ ¼ 104.3 (C-3), 115.4 (C-10), 105.9 (C-50), 110.3
(C-30), 115.4 (C-10), 120.0 (C-5), 123.6 (C-4a), 123.9 (C-8),
129.7 (C-6), 131.8 (C-7), 132.4 (C-60), 131.7 (C-40), 140.4
(C-8a), 148.0 (C-2), 157.4 (C-20), 160.0 (C-4) ppm; IR
þ
m=z (%) ¼ 235 (M ꢁ, 100), 234 (78), 226 (9), 167 (44), 133
(39), 100 (26), 77 (12).
20-Aminoflavone (6a)
1
Mp: 311–312ꢅC; H and 13C NMR data see Ref. [20]; IR
(KBr): ꢃꢀ¼ 1644, 1602, 1565, 1459, 1373, 1128, 752 cmꢆ1
;
(KBr): ꢃꢀ¼ 1594, 1566, 1478, 1438, 1221, 1090, 824,
þ
757 cmꢆ1
þ
; MS (EI, 70eV): m=z (%) ¼ 267 (M ꢁ, 100), 266
MS (EI, 70 eV): m=z (%) ¼ 237 (M ꢁ, 100), 236 (17), 221 (6),
(48), 237 (16), 209 (25), 183 (10), 141 (12), 136 (15), 97 (39),
83 (47), 77 (10).
209 (16), 180 (3), 121 (5), 117 (56), 105 (5), 92 (10), 63 (7).
20-Amino-7-methoxyflavone (6b)
Mp: 172–174ꢅC; 1H and 1þ3C NMR data see Ref. [20]; MS (EI,
2-(2-Hydroxy-6-methoxyphenyl)-4-hydroxyquinoline
70eV): m=z (%) ¼ 267 (M ꢁ, 100), 266 (18), 251 (5), 239 (15),
(8c, C16H13NO3)
Mp: 120–121ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 3.75 (s,
OCH3), 6.43 (br s, H-3), 6.60 (d, J ¼ 8.1 Hz, H-30), 6.63 (d,
J ¼ 8.1 Hz, H-50), 7.30 (t, J ¼ 8.1 Hz, H-40), 7.56 (t, J ¼ 7.7 Hz,
H-6), 7.83 (t, J ¼ 7.7 Hz, H-7), 8.20 (d, J ¼ 7.7 Hz, H-5, H-8),
11.24 (br s, OH) ppm; 13C NMR (75 MHz, DMSO-d6):
ꢁ ¼ 55.7 (OCH3), 102.1 (C-3 and C-50), 109.0 (C-30), 110.2
(C-10), 116.7 (C-5), 123.2 (C-8), 123.8 (C-4a), 131.1 (C-40),
131.6 (C-6 and C-7), 140.1 (C-8a), 146.4 (C-2 and C-60),
157.8 (C-4 and C-20) ppm; IR (KBr): ꢃꢀ¼ 1602, 1562, 1479,
1392, 1334, 1þ301, 1178, 823, 755cmꢆ1; MS (EI 70eV): m=z
(%) ¼ 267 (M ꢁ, 100), 266 (50), 252 (24), 237 (21), 224 (49),
224 (32), 167 (5), 151 (20), 117 (45), 107 (9), 79 (9), 63 (11).
20-Amino-5-methoxyflavone (6c)
1
Mp: 161–162ꢅC; H and 13C NMR data see Ref. [20]; IR
(KBr): ꢃꢀ¼ 1727, 1629, 1567, 1475, 1434, 1382, 1307, 1268,
þ
1238, 1101, 750 cmꢆ1
; MS (EI, 70eV): m=z (%) ¼ 267 (M ꢁ,
100), 266 (39), 248 (15), 238 (22), 221 (36), 167 (13), 149
(23), 122 (8), 117 (66), 107 (17), 90 (25), 77 (5).
2-(2-Hydroxyphenyl)-4-hydroxyquinoline-N-oxide
(7a, C15H11NO3)
Mp: 189–190ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 6.91 (s
br, H-3), 6.98–7.06 (m, H-30 and H-50), 7.48 (dt, J ¼ 1.3,
7.7 Hz, H-40), 7.55 (d, J ¼ 7.7 Hz, H-60), 7.74 (t, J ¼ 7.7 Hz,
H-6), 7.95 (ddd, J ¼ 0.7, 7.7, 8.6 Hz, H-7), 8.28 (d, J ¼ 7.7 Hz,
H-5), 8.55 (d, J ¼ 8.6 Hz, H-8), 12.00 (br s, OH) ppm; 13C
NMR (75 MHz, DMSO-d6): ꢁ ¼ 106.3 (C-3), 118.4 (C-8),
119.2 and 119.3 (C-30 and C-50), 121.6 (C-4a), 121.8 (C-10),
123.4 (C-5), 127.1 (C-6), 131.2 (C-60), 132.2 (C-40), 132.5
(C-7), 140.2 (C-8a), 149.5 (C-2), 159.1 (C-20 and C-4) ppm;
209 (15), 196 (13), 183 (11), 167 (16), 141 (8), 131 (20), 120
(30), 111 (10), 97 (9).
Acknowledgements
Thanks are due to the University of Aveiro, University of
´
Tras-os-Montes e Alto Douro, FEDER and FCT-Portugal
(Organic Chemistry Research Unit – no. 62) for funding.
IR (KBr): ꢃꢀ¼ 1598, 1546, 1455, 1409, 1201, 1091, 806,
þ
757 cmꢆ1
; MS (EI, 70eV): m=z (%) ¼ 253 (M ꢁ, 35), 237
References
(100), 236 (96), 224 (7), 209 (25), 180 (18), 152 (11), 116
(5), 89 (15), 77 (14), 63 (6).
´
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2-(2-Hydroxyphenyl)-4-hydroxyquinoline (8a, C15H11NO2)
1
Mp: 105–106ꢅC; H NMR (300 MHz, DMSO-d6): ꢁ ¼ 6.57
(s br, H-3), 6.87–6.90 (m, H-30 and H-50), 7.38 (dt, J ¼ 1.5,
7.2 Hz, H-40), 7.46 (dd, J ¼ 1.5, 8.0 Hz, H-60), 7.57 (t,
J ¼ 8.6 Hz, H-6), 7.83–7.87 (m, H-7), 8.26 (dd, J ¼ 0.9,
8.6 Hz, H-8), 8.44 (d, J ¼ 8.6 Hz, H-5), 12.35 (br s, OH)
ppm; 13C NMR (75 MHz, DMSO-d6): ꢁ ¼ 106.5 (C-3), 116.8
(C-10), 118.0 (C-5), 118.3 (C-50), 119.4 (C-30), 122.5 (C-4a),
124.0 (C-8), 125.3 (C-6), 130.9 (C-60), 131.6 (C-7), 131.7
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ppm; IR (KBr): ꢃꢀ¼ 1596, 1546, 1455, 1407, 1201, 1089, 804,
þ
755 cmꢆ1
; MS (EI, 70 eV): m=z (%) ¼ 237 (M ꢁ, 100), 236
[5] Jones G (1996) In: Katritzky AR, Rees CW, Scriven EF
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2-(2-Hydroxy-4-methoxyphenyl)-4-hydroxyquinoline
(8b, C15H11NO2)
Mp: 110–111ꢅC; 1H NMR (300MHz, DMSO-d6): ꢁ ¼ 6.40 (s
br, H-3), 6.50 (d, J ¼ 1.2 Hz, H-30), 6.52 (dd, J ¼ 1.2, 8.0 Hz,
H-50), 7.57 (t, J ¼ 8.0 Hz, H-6), 7.77 (d, J ¼ 8.0 Hz, H-60), 7.80

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