3-aryl-6-methoxy-2-oxo-1,2-dihydroquinoline-4-carbonitriles as solvent and pH independent green fluorescent dyes

Article abstract of DOI:10.1002/jhet.1084

Highly fluorescent and stable 3-aryl-6-methoxy-2-oxoquinoline-4- carbonitriles 6 (λ_exc = 408 nm and λ_em = 510 nm) were synthesized starting from appropriate arylmalonates 2. Ring closure reaction with p-anisidine gave 4-hydroxyquinol

Full text of DOI:10.1002/jhet.1084

November 2012
3-Aryl-6-methoxy-2-oxo-1,2-dihydroquinoline-4-carbonitriles as
Solvent and pH Independent Green Fluorescent Dyes
1415
*
Guy Crépin Enoua, Georg Uray, and Wolfgang Stadlbauer
Division of Organic and Bioorganic Chemistry, Department of Chemistry, Karl-Franzens
University of Graz, A-8010 Graz, Austria/Europe
*
E-mail: wolfgang.stadlbauer@uni-graz.at
Received June 17, 2011
DOI 10.1002/jhet.1084
View this article online at wileyonlinelibrary.com.
Highly fluorescent and stable 3-aryl-6-methoxy-2-oxoquinoline-4-carbonitriles 6 (λexc = 408 nm and
em = 510 nm) were synthesized starting from appropriate arylmalonates 2. Ring closure reaction with
λ
p-anisidine gave 4-hydroxyquinolones 3, which could be bis-chlorinated to yield quinolines 4. Regio-
selective hydrolysis produced reactive 4-chloroquinolones 5, which were converted to green fluorescent
4-cyano quinolones 6 using toluenesulfinates as catalysts.
J. Heterocyclic Chem., 49, 1415 (2012).
INTRODUCTION
2-quinolones 3 involves the use of 2-arylmalonates 2,
obtained either by a Claisen condensation reaction type [5],
or via C C couplings of malonates with arylhalogenides
using metal catalysts [6]. We started the reaction from
commercially available arylacetates 1b–d utilizing the Claisen
condensation pathway. The literature describes several
variants for the preparation of 2 by Claisen condensation
from 1, e.g., via oxaloesters [5a–d], or by condensation
reaction with diethyl carbonate [5e–g] or other similar
methods. In this work, the diethyl carbonate method from
ref. [5f] was applied. Arylmalonates 2b–d were synthesized
from arylacetates 1b–d having a 4-chloro-, a 3-chloro-,
and a 4-methoxy substituent in the aryl ring. The reaction
with diethyl carbonate was promoted by sodium hydride
as a strong base and gave yields within 48–83% (Scheme 1).
The arylmalonates 2a–d readily underwent cyclization
with p-anisidine to 3-aryl-4-hydroxy-6-methoxy-2(1H)-
quinolones 3a–d in 73–98% yields. The cyclocondensation
step is known to proceed in two steps, having as the key
reaction the thermolytic formation of a ketene intermediate
[7], which attacks easily the aryl nucleus at elevated tempera-
tures and gives the quinoline ring by cyclization reaction. In
the same manner, 3-methyl- and 3-ethyl-4-hydroxy-6-meth-
oxy-2(1H)-quinolones 3e,f were obtained from 2-methyl- or
2-ethylmalonates 2e,f and p-anisidine in 94 and 43% yield,
We have shown that 6,7-dimethoxy-4-trifluoromethyl-
carbostyrils [1] and 4-cyano-6,7-dimethoxycarbostyrils
[2] are highly fluorescent dyes. Compared with previously
known substitution patterns they show red-shifted
absorption and emission wavelengths up to 410 and
460 nm, respectively. Together with quantum yields
up to 0.6, these parameters are fairly solvent and pH
independent. Hence, they are suitable to outclass widely
used coumarin dyes [3]. Furthermore, these 6,7-4 push–
pull substituted quinolone dyes show high thermal and
photochemical stability and no oxygen quenching
different from many other fluorophores. Recently,
another work group incorporated our 4-trifluoromethyl
and 4-cyanocarbostyrils into peptides and got an efficient
fluorescence-resonance-energy transfer (FRET) system [4].
In this communication, we describe an investigation on 6-
methoxy-2-oxo-1,2-dihydro-quinoline-4-carbonitriles (4-cyano-
6-methoxycarbostyrils) having 3-aryl- and 3-alkyl substituents,
and compare the electronic spectra with the 6,7-dimethoxy
derivatives. Synthesis of 3-aryl and 3-alkyl-4-hydroxy-6-
methoxy-2-quinolones 3 was planned to proceed via the reaction
of corresponding aryl- and alkylmalonates with p-anisidine.
Final conversion of the 4-hydroxy to the cyano group should
give strongly fluorescent carbostyril derivatives 6.
1
respectively. H NMR spectroscopic data proved the struc-
tures by the singlet signals of 1-NH and 4-OH (∼ 10.20 and
∼ 11.30 ppm) and by the 5-H, 7-H, and 8-H signals
(∼ 7.35 ppm, doublet with 2.5 Hz; ∼ 7.15 ppm, doubled dou-
blet with 9 and 2.5 Hz; ∼ 7.25 ppm, doublet with 9 Hz), to-
gether with the 6-methoxy signal as a singlet at ∼ 3.80 ppm.
RESULTS AND DISCUSSION
Synthesis. The key step in the reaction sequence for
the ring closure reaction to 3-aryl-4-hydroxy-6-methoxy-
© 2012 HeteroCorporation

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G. C. Enoua, G. Uray, and W. Stadlbauer
Vol 49
Scheme 1
Scheme 2
because a single substitution of the 4-hydroxy group of 3 to
a 4-chloro-substituent in 5 could not be performed regiose-
lectively: with phosphoryl chloride, in all attempts also the
enolizable 2-oxo group was replaced at least partially by
chlorination, and the completion of the reaction resulted
in the formation of 2,4-dichloroquinolines 4a–f in excel-
lent yields, confirmed by the lack of the carbonyl function
in position 2 in the IR spectra. The reaction time for a com-
plete conversion was strongly dependent on the substituent
in position 3: the 3-aryl substituent caused a rather high
The next step in our reaction sequence was the introduc-
tion of a usable leaving group in position 4 instead of the 4-
hydroxy group in quinolone 3. In earlier investigations, we
found a 4-chloro substituent to have the best properties,
both in the synthesis and stability, and then in further
exchange reactions [2]. The transformation to the desired
reactive 4-chloroquinolone 5 was achieved in two steps,
Scheme 3
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DOI 10.1002/jhet

November 2012
3-Aryl-6-methoxy-2-oxo-1,2-dihydroquinoline-4-carbonitriles as Solvent and pH
Independent Green Fluorescent Dyes
1417
Scheme 4
methods, and no conversion to any fluorescent new compound
could be detected (Scheme 3).
The chlorination of cyanoquinolone 6a gave in excellent
yields the 2-chloroquinoline-4-carbonitrile 7. No reaction
took place at the 4-position, which is visible in the IR spec-
tra, because the 2-carbonyl signal disappeared, whereas the
nitrile signal at 2236 cm−1 remained unchanged. This
shows the stability of this class of compounds 6, which
makes them useful as stable fluorescent probes. The strong
fluorescence of 6a disappeared nearly completely when the
compound was converted to quinoline 7, which demon-
strates the importance of the carbostyril (2-quinolone)
structure element for fluorescence properties.
Electronic spectra. The aim of this investigation was the
comparison of 3-aryl-4-cyano-6-methoxy-carbostyrils 6
having different substituents at the 3-aryl ring, to get
information on the influence of substituents in 3-position
on the fluorescence properties of this compound class.
This class of compounds was hitherto not described by
other groups. In ref. [2], we have described one similar
type of compounds, 6,7-dimethoxy-1-methyl-2-oxo-3-
phenyl-1,2-dihydroquinoline-4-carbonitriles 8. Fluorescence
measurement of these compounds shows an excitation
wavelength of λexc = 380–390 nm and an emission
wavelength of λem = 480–490 nm, which means a red shift
of about 50 nm caused by the phenyl group, compared with
3-unsubstituted 6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-4-
carbonitriles 9 (λexc at 380–390 nm, λem at 430–440 nm;
Scheme 4).
Surprisingly, compared with 6,7-dimethoxy derivatives 8
the single 6-methoxy group in this 4-cyano-3-phenylcarbo-
styrils 6 causes a more efficient red shift. Already 4-hydroxy-
6-methoxy-3-(4-chlorophenyl)-carbostyril (3b) shows a blue
fluorescence with λexc at 352 nm and λem at 416 nm.
6-Methoxy-2-oxo-3-phenyl-1,2-dihydroquinoline-4-car-
bonitrile (6a) with no substituent in the 3-aryl ring shows
fluorescence values of λexc at 405 nm and λem at 505 nm;
a similar value (λexc at 405 nm and λem at 503 nm) was
observed with the 4-methoxyphenyl derivative 6d. Both
chlorophenyl derivatives 6b and 6c gave slightly red
shifted values (λexc at 406 and 408 nm, and λem at 510 nm),
but no significant change in the wavelengths was visible as
one could assume. Investigations in different solvents
revealed that electronic spectra of structures 6 are almost
not influenced (e.g., λem at 505 nm in DMSO, and λem at
500 nm in water for 6d), and also no pH dependence and
oxygen quenching was observed.
reactivity with best results observed in the phenyl and p-
chlorophenyl derivatives 3a,b, similar but lower reactivity
in p-methoxy- and m-chlorophenyl derivatives 3c,d
and rather low reactivity in the 3-alkyl derivatives 3e,f
(Scheme 2).
As shown in earlier investigations [2], it is possible to
hydrolyze regioselectively the chloro function in position
2 of dichloroquinolines 4 in acidic media such as methane-
sulfonic acid to get back the 2-oxo function. The slightly
lower reactivity of 4 caused probably by the 6-methoxy
group demanded higher reaction temperatures: so we
replaced the solvent ethanol by n-butanol, which allowed
us to convert the dichloro derivatives 4 in good to excellent
yields to 4-chloro-2-quinolones 5a–f. The infrared spectral
data of 5 revealed the 2-oxo-function (∼ 1650 cm−1), and
1
in the H NMR spectra the NH signals were visible again
at ∼ 12.00 ppm. 4-Chloroquinolones 5 should now serve
as reactive starting material for the introduction of the cy-
ano substituent in position 4.
A simple nucleophilic substitution of the 4-chloro function
in 5 by the cyano group using a reaction with potassium or
sodium cyanide was unsuccessful, also in the presence of
different crown ethers. Attempts with the Rosenmund–Braun
aromatic cyanation [8] with copper(I) cyanide gave a mixture
of fluorescent compounds, but separation attempts failed. A
method we have recently used successfully for such reactions
[2] was the addition of sodium p-toluenesulfinate as reaction
mediator to the reaction mixture of 4-chloroquinolones and
potassium cyanide in dimethylformamide. The application of
this method in the reaction of 5 gave with all 3-arylsubstituted
quinolones 5a–d the 4-cyanoquinolones 6a–d in excellent
yields. The different substituents at the aryl moiety did not
affect the reactivity and yield of 5a–d. The successful exchange
was already visible in the TLC control: the newly formed
cyano product 6 gave a strong greenish fluorescent spot, which
made it easy to follow the reaction. IR spectra showed besides
the strong carbonyl signal at about 1660 cm−1 a weak signal for
CONCLUSIONS
1
the cyano group at about 2230 cm−1. The H and 13C NMR
The synthesis of 6-methoxy-2-oxo-3-aryl-1,2-dihydro-
quinoline-4-carbonitriles 6 could be performed in a five-
step synthesis starting from arylacetates 1 in a good overall
yield. The resulting quinoline-4-carbonitriles 6 showed
spectra showed all relevant signals, and mass spectra using
either APCI or ESI methods gave the parent peaks with
100%. On the other hand, however, the exchange of the chloro
group in 3-alkylquinolones 5e,f was unsuccessful with all
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G. C. Enoua, G. Uray, and W. Stadlbauer
Vol 49
59.0 mL, 487 mmol) in dry tetrahydrofuran (120 mL), was
added dropwise a solution of the appropriate ethyl arylacetate
1b–d (95 mmol) in dry tetrahydrofuran (40 mL). The mixture
was heated under reflux for the time given, cooled to 20°C, and
neutralized with a saturated aq. ammonium chloride (150 mL).
The organic phase was separated and the aqueous phase
extracted with diethylether (2 × 150 mL). The combined
organic phases were washed with saturated aq. NaHCO3 (150
mL) and brine (150 mL), and dried over sodium sulfate. The
solvent was removed under reduced pressure and the residue
purified by distillation under reduced pressure.
Diethyl (4-chlorophenyl)malonate (2b). From (4-chlorophenyl)
acetate 1b (18.85 g, 95 mmol; reaction time: 2 h). The yield
was 21.34 g (83%), colorless oil, bp 170–180°C/27 mbar, lit.
bp 116–180°C/0.05–25 mmHg [5c,e,g, 6a, 10b–d].
Diethyl (3-chlorophenyl)malonate (2c). From (3-chlorophenyl)
acetate 1c (18.85 g, 95 mmol; reaction time: 7 h), the yield was
12.34 g (48%), colorless oil, bp 178–184°C/22.7 mbar, lit. bp
145–178°C/1.2–17 mmHg [5c,f, 6a,b,i].
Diethyl (4-methoxyphenyl)malonate (2d). From (4-
methoxyphenyl)acetate 1d (18.35 g, 95 mmol; reaction
time: 87 h), the yield was 17.37 g (69%), clear yellow
oil, bp 190–206°C/36.5 mbar, lit. bp 136–198°C/0.05–13
mmHg [5d,i, 6d–h, 10a, 11a–c].
Diethyl methylmalonate (2e) and diethyl ethylmalonate
(2f). Diethyl methylmalonate (2e) and diethyl ethylmalonate (2f)
are commercially available.
very useful fluorescence properties: Excitation is possible
in visible light (above 400 nm), and emission can be
measured above 500 nm (in the green region), which
means a Stokes’ shift of about 100 nm. The introduction
of electron-pushing or pulling substituents at the 3-aryl
ring has no significant effect on the fluorescence values
of 6a–d. One disadvantage of the 6-methoxycarbostyril
substitution pattern was observed throughout: compared
with dimethoxy derivatives 8 and 9 (Φ = 0.5 and 0.4),
in 3-aryl-6-methoxy derivatives 6 fluorescence quantum
yields are lower (Φ = 0.05–0.23).
EXPERIMENTAL
General. Melting points were determined in open capillary
tubes using a Stuart SMP3 Melting Point Apparatus. IR spectra
were recorded with a Mattson Galaxy Series FTIR 7020
instrument in potassium bromide discs, or with a Bruker Alpha-P
with attenuated total reflectance (ATR) measurement, using
a reflexion method. NMR spectra were recorded on a Bruker
AMX 360 instrument (360 MHz 1H, 90 MHz 13C), or on a
Bruker Avance III instrument (300 MHz 1H), or on a Bruker
Avance DRX 500 instrument (500 MHz 1H, 125 MHz 13C).
Chemical shifts are given in ppm (δ) from the internal TMS
standard. Elemental analyses were performed at the
Microanalytical Laboratory of the University of Vienna,
Austria. Mass spectra were obtained from a HP 1100 LC/MSD
mass spectral instrument (positive or negative APCI ion source,
50–200 V, nitrogen, or AP-ES electrospray method). UV/Vis
spectra were recorded with a Shimadzu UV/Vis scanning
spectrophotometer UV-2101 PC; concentration: 1 × 10−4 M.
Fluorescence data: Excitation and emission spectra were
recorded with a Perkin-Elmer LS50B luminescence spectrometer.
Determination of quantum yields: emission signals were set in
relation to the known area of the emission signal of quinine
sulfate at pH = 1. Corrections were made for other solvents by
using the factor (nwater/nsolvent)2 [3c,e]. Analytical HPLC
was performed on a Shimadzu LC 20 system equipped with a
diode array detector (215 and 254 nm) on a Pathfinder AS
reversed phase (4.6150 mm, 5 μm) column, running an
acetonitrile/water gradient (30–100% acetonitrile). Dry column
flash chromatography [9] was carried out on silica gel 60 H
(5–40 μm) (Merck, Darmstadt, Germany). All reactions were
monitored by thin layer chromatography on 0.2-mm silica gel
F 254 plates (Merck, Darmstadt, Germany) using UV light
(254 and 366 nm) for detection. Common reagent-grade
chemicals are either commercially available and were used
without further purification or prepared by standard literature
procedures.
4-Hydroxy-6-methoxy-3-phenylquinolin-2(1H)-one (3a).
A
solution of p-anisidine (10.01 g, 81.4 mmol) and
phenylmalonate 2a (19.34 g, 82 mmol) in diphenyl ether (50
mL) was heated under reflux at about 250–300°C for 3 h.
During this time, ethanol (6.0 mL, 103 mmol) was liberated.
The solution was cooled to 20°C, diluted with cyclohexane
(25 mL) and filtered by suction. The solid was dissolved in
warm aq. sodium hydroxide (250 mL, 1M) and filtered. To
the alkaline filtrate, concentrated hydrochloric acid was
added until pH = 1–2 was reached, the precipitate filtered by
suction, washed with water, and dried at 40°C under reduced
pressure. The yield was 21.09 g (97%), colorless prisms, mp
324–327°C (ethanol), lit. mp 319–326°C [12b].
3-(4-Chlorophenyl)-4-hydroxy-6-methoxyquinolin-2(1H)-one
(3b). p-Anisidine (1.68 g, 13.7 mmol) and p-chlorophenyl malonate
2b (3.70 g, 13.7 mmol) in diphenyl ether (16 mL) were brought to
reaction and worked up as described for 3a. The yield was 3.27 g
(79%), colorless prisms, mp 347–355°C (ethanol). IR (KBr): 2949
s, 1648 s (amide-C O), 1607 s, 1585 s cm−1. 1H NMR (300 MHz;
DMSO-d6): δ 3.79 (s, 3 H, MeO), 7.17 (dd, J = 8.9 + 2.7 Hz, 1
H, 7-H), 7.24 (d, J = 8.9 Hz, 1 H, 8-H), 7.39 (d, J = 8.8 Hz, 2 H,
ArHAA′), 7.44 (d, J = 2.6 Hz, 1 H, 5-H), 7.45 (d, J = 8.8 Hz, 2 H,
ArHBB’), 10.20 (s, 1 H, 1-NH), 11.42 (s, 1 H, OH). UV (DMSO):
λ (ε, M−1 cm−1) = 352 (8720) nm. Fluorescence (DMSO):
λ (ΦF) = 416 (0.03). Anal. calcd for C16H12ClNO3 (301.73): C,
63.69; H, 4.01; N, 4.64. Found: C, 63.56; H, 3.83; N, 4.63.
3-(3-Chlorophenyl)-4-hydroxy-6-methoxyquinolin-2(1H)-one
(3c). p-Anisidine (5.27 g, 42.9 mmol) and m-chlorophenyl malonate
2c (11.59 g, 42.9 mmol) in diphenyl ether (50 mL) were brought to
reaction and worked up as described for 3a. The yield was 9.41 g
(73%), colorless prisms, mp 322–325°C (ethanol). IR (KBr): 2964
s, 1644 m (amide-C O), 1607 s, 1587 w cm−1. 1H NMR (300
MHz; DMSO-d6): δ 3.79 (s, 3 H, MeO), 7.18 (dd, J = 8.9 + 2.4
Hz, 1 H, 7-H), 7.25 (d, J = 8.9 Hz, 1 H, 8-H), 7.37 (s, 1 H, ArH),
7.34–7.42 (m, 3 H, ArH), 7.45 (d, J = 2.0 Hz, 1 H, 5-H), 10.30 (s,
Ethyl (4-chlorophenyl)acetate (1b), ethyl (3-chlorophenyl)
acetate (1c), and ethyl (4-methoxyphenyl)acetate (1d). Ethyl
(4-chlorophenyl)acetate (1b), ethyl (3-chlorophenyl)acetate (1c),
and ethyl (4-methoxyphenyl)acetate (1d) are commercially
available.
Diethyl phenylmalonate (2a). Diethyl phenylmalonate (2a) is
commercially available.
General procedure for the preparation of diethyl
arylmalonates (2b–d). To a mixture of sodium hydride (60% in
mineral oil; 15.00 g, 375 mmol) and diethyl carbonate (57.50 g,
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3-Aryl-6-methoxy-2-oxo-1,2-dihydroquinoline-4-carbonitriles as Solvent and pH
Independent Green Fluorescent Dyes
1419
1 H, NH), 11.44 (s, 1 H, OH). Anal. calcd for C16H12ClNO3
(301.73): C, 63.69; H, 4.01; N 4.64. Found: C, 63.67; H, 3.78; N,
4.63.
(ethanol). IR (KBr): 3073 w, 1618 w, 1599 s, 1567 m cm−1
.
1H NMR (300 MHz; DMSO-d6): δ 3.97 (s, 3 H, MeO), 7.41–
7.42 (m, 1 H, ArH), 7.48 (d, J = 2.6 Hz, 1 H, 5-H), 7.58–7.60
(m, 3 H, ArH), 7.62 (dd, J = 9.2 + 2.6 Hz, 1 H, 7-H), 8.02
(d, J = 9.2 Hz, 1 H, 8-H). Anal. calcd for C16H10Cl3NO
(338.62): C, 56.75; H, 2.98; N, 4.14. Found: C, 56.46; H, 2.66;
N, 4.09.
4-Hydroxy-6-methoxy-3-(4-methoxyphenyl)quinolin-2(1H)-
one (3d). p-Anisidine (5.30 g, 43.1 mmol) and (p-methoxyphenyl)
malonate 2d (11.46 g, 42.8 mmol) in diphenyl ether (50 mL) were
brought to reaction and worked up as described for 3a. The yield
was 12.59 g (98%), colorless prisms, mp 325–328°C (ethanol).
IR: 3435 m, 2958 m, 1647 m (amide-C O), 1611 s, 1587 w cm−1.
1H NMR (300 MHz; DMSO-d6): δ 3.78 (s, 3 H, 6-MeO), 3.79
(s, 3 H, Ar-MeO), 6.96 (d, J = 8.8 Hz, 2 H, ArHBB′), 7.14 (dd,
J = 8.9 + 2.7 Hz, 1 H, 7-H), 7.23 (d, J = 8.9 Hz, 1 H, 8-H),
7.30 (d, J = 8.8 Hz, 2 H, ArHAA′), 7.44 (d, J = 2.6 Hz, 1 H,
5-H), 10.00 (s, 1 H, NH), 11.33 (s, 1 H, OH). Anal. calcd for
C17H15NO4 (297.31): C, 68.68, H, 5.09; N 4.71. Found: C,
68.31; H, 4.86; N, 4.72.
2,4-Dichloro-6-methoxy-3-(4-methoxyphenyl)quinoline
(4d). 3-(4-Methoxyphenyl)quinolone 3d (11.10 g, 37.4 mmol) in
phosphorylchloride (45 mL) was brought to reaction (reaction
time: 12 h) and worked up as described for 4a. The yield was
9.77 g (79%), colorless prisms, mp 169–170°C (ethanol). IR:
1
3439 s, 1617 s, 1565 m cm−1. H NMR (300 MHz; DMSO-d6):
δ 3.83 (s, 3 H, 6-MeO), 3.95 (s, 3 H, Ar-MeO), 7.08 (d, J = 8.7 Hz,
2 H, ArHBB’), 7.32 (d, J = 8.6 Hz, 2 H, ArHAA’), 7.44 (d, J = 2.6 Hz,
1 H, 5-H), 7.56 (dd, J = 9.2 + 2.7 Hz, 1 H, 7-H), 7.97 (d, J = 9.2 Hz,
1 H, 8-H). Anal. calcd for C17H13Cl2NO2 (334.20): C, 61.10; H,
3.92; N, 4.19. Found: C, 61.08; H, 3.72; N, 4.17.
4-Hydroxy-6-methoxy-3-methylquinolin-2(1H)-one (3e). p-
Anisidine (10.00 g, 81.3 mmol) and methylmalonate 2e (14.0
mL, 81 mmol) in diphenyl ether (50 mL) were brought to
reaction and worked up as described for 3a. The yield was
15.71 g (94%), colorless prisms, mp 234–236°C (ethanol). IR:
2,4-Dichloro-6-methoxy-3-methyl-quinoline (4e). 3-
Methylquinolone 3e (9.50 g, 46.3 mmol) in phosphorylchloride
(54 mL) was brought to reaction (reaction time: 24 h) and worked
up as described for 4a. The yield was 10.28 g (92%), light
yellow prisms, mp 149–151°C (ethanol). IR (KBr): 3459 s,
1
3431 s, 1647 s (amide-C O), 1612 s cm−1. H NMR (300 MHz;
DMSO-d6): δ 1.99 (s, 3 H, Me), 3.78 (s, 3 H, MeO), 7.08 (dd,
J = 8.9 + 2.7 Hz, 1 H, 7-H), 7.19 (d, J = 8.9 Hz, 1 H, 8-H),
7.34 (d, J = 2.7 Hz, 1 H, 5-H), 10.03 (s, 1 H, NH), 11.22 (s, 1 H,
OH). Anal. calcd for C11H11NO3 (205.22): C, 64.38; H, 5.40; N,
6.83. Found: C, 64.32; H, 5.26; N, 6.85.
3-Ethyl-4-hydroxy-6-methoxyquinolin-2(1H)-one (3f). p-
Anisidine (12.50 g, 101 mmol) and diethyl ethylmalonate (2f:
18.0 mL, 101 mmol) in diphenyl ether (50 mL) were brought to
reaction and worked up as described for 3a. The yield was 9.50
g (43%), colorless prisms, mp 160–162°C (ethanol), lit. mp
172°C [12a].
1622 m, 1572 w cm−1 1H NMR (300 MHz, DMSO-d6): δ
.
2.60 (s, 3 H, Me), 3.95 (s, 3 H, MeO), 7.40 (d, J = 2.7 Hz, 1
H, 5-H), 7.49 (dd, J = 9.2 + 2.8 Hz, 1 H, 7-H), 7.91 (d, J = 9.1 Hz,
1 H, 8-H). Anal. calcd for C11H9Cl2NO (242.11): C, 54.57; H,
3.75; N, 5.79. Found: C, 54.36; H, 3.55; N, 5.69.
2,4-Dichloro-3-ethyl-6-methoxyquinoline (4f). 3-Ethylquinolone
3f (3.15 g, 14.4 mmol) in phosphorylchloride (17 mL) was brought
to reaction (reaction time: 24 h) and worked up as described for 4a.
The yield was 3.09 g (84%), colorless prisms, mp 115–118°C
1
(ethanol). IR (ATR): 3038 w, 1619 m, 1568 m cm−1. H NMR
2,4-Dichloro-6-methoxy-3-phenylquinoline (4a). A solution of 3-
phenylquinolone 3a (18.50 g, 69.3 mmol) in phosphorylchloride
(80 mL) was heated under reflux for 8 h. The excess of
phosphorylchloride was removed under reduced pressure, the residue
poured onto ice/water (300 mL), brought to pH = 4–6 with aq.
sodium hydroxide (5 M), filtered by suction, and washed with water.
The solid was dried at 40°C under reduced pressure. The yield was
20.41 g (97%), colorless prisms, mp 220–222°C (ethanol). IR (KBr):
(300 MHz, DMSO-d6): δ 1.20 (t, J = 7.4 Hz, 3 H, Me), 3.00 (q,
J = 7.2 Hz, 2 H, CH2), 3.94 (s, 3 H, MeO), 7.35 (s, 1 H, 5-H),
7.47 (d, J = 8.8 Hz, 7-H), 7.86 (d, J = 8.8 Hz, 1 H, 8-H). 13C
NMR (90 MHz, DMSO-d6): δ 12.8 (Me), 25.3 (MeO), 56.2
(CH2), 102.6 (ArC), 123.7 (ArC), 126.9 (ArC), 130.5 (ArC),
133.6 (ArC), 140.6 (4-C), 141.8 (9-C), 147.8 (2-C), 159.3 (6-C).
Anal. calcd for C12H11Cl2NO (256.13): C, 56.27, H, 4.33; N;
5.47. Found: C, 56.10; H, 4.13; N, 5.43.
1
3438 m, 1620 m, 1572 m cm−1. H NMR (300 MHz, DMSO-d6):
4-Chloro-6-methoxy-3-phenylquinolin-2(1H)-one (5a). 3-
Phenylquinoline 4d (7.00 g, 23.0 mmol) and methanesulfonic
acid (11.5 mL, 70% in water) in 1-butanol (100 mL) were
heated under reflux for 30 h. The mixture was cooled to 20°C,
poured into ice/water (100 mL), and brought to pH = 4–6 with
sodium hydroxide (2 M). The solid was filtered off by suction,
washed with water, and dried at 40°C under reduced pressure.
The yield was 5.86 g (89%), colorless prisms, mp 278–281°C
(ethanol). IR (ATR): 3437 m, 3192 s, 1640 s (amide-C O), 1595
δ = 3.97 (s, 3 H, MeO), 7.39–7.40 (m, 1 H, 7-H), 7.42 (d, J = 1.8
Hz, 1 H, 5-H), 7.48–7.62 (m, 5 H, PhH), 8.02 (d, J = 9.2 Hz, 1 H,
8-H). Anal. calcd for C16H11Cl2NO (304.18): C, 63.18; H, 3.65; N,
4.60. Found: C, 63.05; H, 3.44; N, 4.58.
2,4-Dichloro-3-(4-chlorophenyl)-6-methoxyquinoline (4b).
3-(4-Chlorophenyl)quinolone 3b (13.38 g, 44.4 mmol) in
phosphorylchloride (70 mL) was brought to reaction (reaction
time: 8 h) and worked up as described for 4a. The yield was
12.91 g (86%), colorless prisms, mp 167–170°C (ethanol). IR
m cm−1 1H NMR (300 MHz, DMSO-d6): δ 3.38 (s, 3 H,
.
MeO), 7.29–7.48 (m, 8 H, 5-H, 7-H 8-H, PhH), 12.14 (s, 1 H,
NH). Anal. calcd for C16H12ClNO2 (285.73): C, 67.26; H, 4.23;
N, 4.90. Found: C, 67.25; H, 3.99; N, 4.90.
1
(KBr): 3503 w, 1687 w, 1619 s, 1567 m cm−1. H NMR (300
MHz; DMSO-d6): δ 3.96 (s, 3 H, MeO), 7.45 (d, J = 1.8 Hz, 1
H, 5-H), 7.47 (d, J = 8.2 Hz, 2 H, ArHBB’), 7.59 (d, J = 9,2 +
2.0 Hz, 1 H, 7-H), 7.63 (d, J = 8.2 Hz, 2 H, ArHAA’), 7.99 (d,
J = 9.2 Hz, 1 H, 8-H). Anal. calcd for C16H10Cl3NO (338.62):
C, 56.75; H, 2.98; N, 4.14. Found: C, 56.70; H, 2.77; N, 4.14.
2,4-Dichloro-3-(3-chlorophenyl)-6-methoxyquinoline (4c).
3-(3-Chlorophenyl)-6-methoxyquinolone 3c (7.00 g, 23.2
mmol) in phosphorylchloride (30 mL) was brought to reaction
(reaction time: 12 h) and worked up as described for 4a. The
yield was 7.60 g (97%), beige prisms, mp 215–217°C
4-Chloro-3-(4-chlorophenyl)-6-methoxyquinolin-2(1H)-one
(5b). 3-(4-Chlorophenyl)quinoline 4b (6.00 g, 17.7 mmol) and
methanesulfonic acid (6.0 mL, 70% in water) in 1-butanol (60
mL) were heated under reflux for 45 h and worked up following
the method described for 5a. The yield was 5.33 g (94%) beige
prisms, mp 296–298°C (ethanol). IR (KBr): 3427 m, 2848 s,
1666 s (amide-C O), 1624 w, 1593 w cm−1 1H NMR (300
.
MHz, DMSO-d6): δ 3.83 (s, 3 H, MeO), 7.30–7.35 (m. 3 H, 5-
Journal of Heterocyclic Chemistry
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G. C. Enoua, G. Uray, and W. Stadlbauer
Vol 49
H, 7-H and 8–H), 7.49 (d, J = 7.7 Hz, 2 H, ArHAA’), 7.52 (d, J =
7.8 Hz, 2 H, ArHBB’), 12.18 (s, 1 H, NH). Anal. calcd for
C16H11Cl2NO2 (320.18): C 60.02, H 3.46, N 4.37. Found: C
60.23, H 3.39, N 4.36.
off by suction, washed with water and dried at 40°C under reduced
pressure. The yield was 2.76 g (95 %), yellow prisms, mp 263–265°
C (acetone). IR (KBr): 3449 s, 2849 m, 2236 w (CN), 1667 s
(amide-C O), 1624 w, 1602 w cm−1. 1H NMR (300 MHz, DMSO-d6):
δ 3.82 (s, 3 H, MeO), 7.11 (d, J = 2.5 Hz, 1 H, 5-H), 7.30
(dd, J = 9.0 + 2.6 Hz, 1 H, 7-H), 7.35 (d, J = 9.0 Hz, 1 H, 8-H),
7.48–7.50 (m, 3 H, PhH), 7.59 (dd, J = 7.5 + 2.4 Hz, 2 H, PhH),
12.44 (s, 1 H, NH). 13C NMR (90 MHz, DMSO-d6): δ 55.9 (Me),
106.6 (ArC), 115.2 (ArC), 117.7 (ArC), 119.2 (CN), 121.5 (ArC),
128.4 (PhC), 129.8 (2 ArCAA’), 130.4 (2 ArCBB’), 133.2 (9-C),
133.7 (PhC), 141.1 (3-C), 155.4 (6-C O), 159.3 (amide-C O at C-2).
UV (DMSO): λ (ε, M–1 cm–1) = 402 (4850) nm; UV (water):
λ (ε, M−1 cm−1) = 400 (5100) nm. Fluorescence (DMSO):
λ (ΦF) = 505 (0.06); Fluorescence (water): λ (ΦF) = 500 (0.05).
MS (APCI, pos): m/z (%) = 277 (100, M + 1). MS (APCI,
neg): m/z (%) = 276 (19, M), 275 (100, M − 1). Anal. calcd for
C17H12N2O2 (276.30): C, 73.90; H, 4.38; N, 10.14. Found: C,
73.62; H, 4.11; N, 9.92.
4-Chloro-3-(3-chlorophenyl)-6-methoxyquinolin-2(1H)-one
(5c). 3-(3-Chlorophenyl)quinoline 4c (6.00 g, 17.7 mmol), and
methanesulfonic acid (3.0 mL, 70% in water) in 1-butanol (50
mL) were heated under reflux for 45 h and worked up following
the method described for 5a. The yield was 5.10 g (90%), beige
prisms, mp 285–288°C (ethanol). IR (KBr): 2832 w, 1658 s
(amide-C O), 1623 m, 1500 m cm−1 1H NMR (300 MHz,
.
DMSO-d6): δ 3.83 (s, 3 H, MeO), 7.32–7.33 (m, 3 H, ArH),
7.37 (d, J = 8.6 Hz, 1 H, 8-H), 7.44 (s, 1 H, ArH), 7.43–7.50
(m, 2 H, 5-H, and 7-H), 12.21 (s, 1 H, NH). Anal. calcd for
C16H11Cl2NO2 (320.18): C, 60.02; H, 3.46; N, 4.37. Found: C,
59.90; H, 3.31; N, 4.35.
4-Chloro-6-methoxy-3-(4-methoxyphenyl)quinolin-2(1H)-one
(5d). 3-(4-Methoxyphenyl)quinoline 4a (7.40 g, 22.2 mmol) and
methanesulfonic acid (8.0 mL, 70% in water) in 1-butanol (80
mL) were heated under reflux for 48 h and worked up following
the method described for 5a. The yield was 6.47 g (93%), beige
prisms, mp 275–277°C (ethanol). IR (ATR): 3435 m, 3179 m,
3-(4-Chlorophenyl)-6-methoxy-2-oxo-1,2-dihydroquinoline-
4-carbonitrile (6b). A mixture of 3-(4-chlorophenyl)quinolone 5b
(1.60 g, 5.10 mmol), sodium p-toluenesulfinate (0.89 g, 5.10
mmol), and dry potassium cyanide (0.81 g, 12.51 mmol) in dry
dimethylformamide (30 mL) was heated to 120°C for 63 h and
worked up following the method described for 6a. The yield was
1.52 g (98 %), yellow prisms, mp 332–333.5°C (acetone). IR
(ATR): 3434 m, 2231 w (CN), 1670 s (amide-C O), 1623 w,
1
1649 s (amide-C O), 1622 w, 1609 w, 1595 w cm−1. H NMR
(300 MHz, DMSO-d6): δ 3.81 (s, 3 H, 6-MeO), 3.83 (s, 3 H,
Ar-MeO), 7.01 (d, J = 8.7 Hz, 2 H, ArHAA′), 7.27–7.36 (m, 5 H,
5-H, 7-H, 8-H, ArHBB’), 12.09 (s, 1 H, NH). Anal. calcd for
C17H14ClNO3 (315.76): C, 64.67, H, 4.47, N, 4.44. Found: C,
64.48, H, 4.27, N, 4.42.
1
1607 w, 1595 w cm−1. H NMR (300 MHz, DMSO-d6): δ 3.78
(s, 3 H, MeO), 7.15 (d, J = 2.1 Hz, 1 H, 5-H), 7.35 (dd, J = 9.1 +
2.3 Hz, 1 H, 7-H), 7.41 (d, J = 9.0 Hz, 1 H, 8-H), 7.58 (d, J = 8.6
Hz, 2 H, ArHAA’), 7.63 (d, J = 8.6 Hz, 2 H, ArHBB’), 12.50 (s, 1
H, NH). 13C NMR (90 MHz, DMSO-d6): δ 56.1 (MeO), 106.7
(10-C), 115.2 (5-C), 117.4 (4-C), 117.8 (7-C), 119.5 (CN), 121.8
(8-C), 130.8 (2 ArCBB’), 132.4 (2 ArAA’), 132.6 (9-C), 133.4
(aryl-C), 134.7 (aryl-C), 139.9 (3-C), 155.5 (6-C O), 159.1
(amide-C O at C-2). UV (DMSO): λ (ε, M−1 cm−1) = 311, 406
(9270, 6840) nm. Fluorescence (DMSO): λ (ΦF) = 510 (0.23).
MS (ESI, neg): m/z (%) = 310 (35, M), 309 (100, M − 1). Anal.
calcd. for C17H11ClN2O2 (310.75): C, 65.71; H, 3.57; N, 9.01.
Found: C, 66.09; H, 3.18; N, 8.63.
4-Chloro-6-methoxy-3-methylquinolin-2(1H)-one (5e). 3-
Methylquinoline 4e (8.50 g, 35.1 mmol) and methanesulfonic
acid ( 7.0 mL, 70% in water) in ethanol (80 mL) were heated
under reflux for 48 h and worked up following the method
described for 5a. The yield was 7.19 g (92 %), light yellow
prisms, mp 253–256°C (ethanol). IR (KBr): 3431 m, 2842 m,
1
1649 s (amide-C O), 1625 sh, 1600 sh, 1566 w cm−1. H NMR
(300 MHz, DMSO-d6): δ 2.22 (s, 3 H, Me), 3.81 (s, 3 H,
MeO), 7.18–7.23 (m, 2 H, 5-H and 7-H), 7.30 (d, J = 8.7 Hz, 1
H, 8-H), 11.95 (s, 1 H, NH). Anal. calcd for C11H10ClNO2
(223.66): C, 59.07; H, 4.51; N, 6.26. Found: C, 58.95; H, 4.32;
N, 6.17.
3-(3-Chlorophenyl)-6-methoxy-2-oxo-1,2-dihydroquinoline-4-
carbonitrile (6c). A mixture of 3-(3-chlorophenyl)quinolone 5c
(2.50 g, 7.81 mmol), sodium p-toluenesulfinate (1.60 g, 8.98
mmol) and dry potassium cyanide (1.70 g, 26.2 mmol) in dry
dimethylformamide (50 mL) was heated to 130°C for 43 h and
worked up following the method described for 6a. The yield was
2.35 g (97%), greenish prisms, mp 328–330°C (acetone). IR
(ATR): 2823 m, 2230 w (CN), 1661 s (amide-C O), 1623 m, 1501
4-Chloro-3-ethyl-6-methoxyquinolin-2(1H)-one (5f). 3-
Ethylquinoline 4f (2.15 g, 8.40 mmol) and 70% methanesulfonic
acid (2.0 mL) in 1-butanol (20 mL) was heated under reflux for 48
h and worked up following the method described for 5a. The yield
was 1.59 g (80%), colorless prisms, mp 215–218°C (ethanol). IR
(ATR): 2867 m, 2722 m, 1651 s (amide-C O), 1620 sh, 1597 s
cm−1. 1H NMR (300 MHz, DMSO-d6): δ 1.07 (t, J = 7.4 Hz, 3 H,
Me), 2.72 (q, J = 7.4 Hz, 2 H, CH2), 3.81 (s, 3 H, MeO), 7.19 (dd,
J = 8.7 + 2.8 Hz, 1 H, 7-H), 7.22 (d, J = 2.3 Hz, 1 H, 5-H), 7.28 (d,
J = 8.7 Hz, 1 H, 8-H), 11.95 (s, 1 H, NH). 13C NMR (90 MHz,
DMSO-d6): δ 12.5 (Me), 21.9 (CH2), 55.9 (MeO), 106.5 (ArC),
117.3 (ArC), 118.7 (ArC), 120.2 (ArC), 131.8 (ArC), 134.2 (ArC),
139.8 (4-C), 155.0 (6-C), 160.9 (2-C O). Anal. calcd for
C12H12ClNO2 (237.69): C, 60.64; H, 5.09; N, 5.89. Found: C,
60.43; H, 4.89; N, 5.82.
6-Methoxy-2-oxo-3-phenyl-1,2-dihydroquinoline-4-carbonitrile
(6a). A mixture of 3-phenylquinolone 5a (3.00 g, 10.51 mmol),
sodium p-toluenesulfinate (1.87 g, 10.51 mmol) and dry potassium
cyanide (2.00 g, 30.8 mmol) in dry dimethylformamide (63 mL) was
heated at 120°C for 45 h with vigorous stirring. The solution was
cooled to 20°C, poured into ice/water (100 mL) and acidified with
concentrated hydrochloric acid to pH = 1–2. The solid was filtered
1
w cm−1. H NMR (300 MHz, DMSO-d6): δ 3.86 (s, 3 H, MeO),
7.18 (d, J = 2.0 Hz, 1 H, 5-H), 7.37 (dd, J = 9.1 + 2.3 Hz, 1 H, 7-
H), 7.41 (d, J = 9.0 Hz, 1 H, 8-H), 7.57 (m, 3 H, ArH), 7.70 (s, 1
H, ArH), 12.54 (s, 1 H, NH). UV (DMSO): λ (ε, M−1 cm−1) = 310,
408 (7080, 5500) nm. Fluorescence (DMSO): λ (ΦF) = 510 (0.11).
Anal. calcd for C17H11ClN2O2 (310.74): C, 65.71; H, 3.57; N,
9.01. Found: C, 65.30; H, 3.45; N 8.86.
6-Methoxy-3-(4-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-
4-carbonitrile (6d). A mixture of 3-(4-methoxyphenyl)quinolone 5d
(1.60 g, 5.11 mmol), sodium p-toluenesulfinate (0.91 g, 5.10 mmol),
and dry potassium cyanide (1.00 g, 15.3 mmol) in dry
dimethylformamide (30.0 mL) was heated to 120°C for 72 h and
worked up following the method described for 6a. The yield was
1.50 g (96 %), yellow prisms, mp 275–278°C (acetone). IR (KBr):
3432 m, 2839 m, 2229 w (CN), 1658 s (amide-C O), 1624 m,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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3-Aryl-6-methoxy-2-oxo-1,2-dihydroquinoline-4-carbonitriles as Solvent and pH
Independent Green Fluorescent Dyes
1421
1606 s, 1574 w cm−1. 1H NMR (300 MHz, DMSO-d6): δ 3.84
(s, 3 H, ArOMe), 3.85 (s, 3 H, 6-MeO), 7.06 (d, J = 8.7 Hz, 2
H, ArHBB′), 7.16 (d, J = 2.4 Hz, 1 H, 5-H), 7.32 (dd, J = 9.0 + 2.4
Hz, 1 H, 7-H), 7.38 (d, J = 9.0 Hz, 1 H, 8-H), 7.58 (d, J = 8.6 Hz, 2
H, ArHAA’), 12.41 (s, 1 H, NH). 13C NMR (90 MHz, DMSO-d6): δ
55.7 (MeO at C-6), 55.9 (4-MeO at Ph), 106.6 (ArC), 113.8 (2
ArCAA’), 115.6 (ArC), 117.6 (ArC), 118.3 (CN), 121.2 (ArC),125.7
(ArC), 132.1 (2 ArCBB’), 132.9 (ArC), 140.8 (ArC), 155.4 (6-C O),
159.4 (4-C at Ph), 160.7 (amide-C O at C-2). UV (DMSO): λ (ε,
VCH: Weinheim, 1990; Vol.A15, p155; (m) Krasovitskii, B. M.; Bolotin, B.
M., Eds. Organic Luminescent Materials; Wiley-VCH: Weinheim, 1988; (n)
Siegrist, A. E.; Hefti, H.; Meyer, H. R.; Schmidt, E. Rev Prog Coloration
1987, 17, 39; (o) Brackmann, U. In Lambdachrome Laser Dyes; Lambda Phy-
sik GmbH: Göttingen, 1986; (p) Wolfbeis, O. S. In Molecular Spectroscopy:
Methods and Applications; Schulman, S. G., Ed.; Wiley: New York, 1985;
Chapter 3; (q) Fletcher, A. N.; Bliss, D. E.; Kauffman, J. M. Opt Commun
1983, 47, 57; (r) Gold, H. In Environmental Quality and Safety, Supplement
Volume IV: The Chemistry of Fluorescent Whitening Agents; Anliker, R.;
Müller, G.; Raab, R.; Zinkernagel, R., Eds.; Georg Thieme: Stuttgart, 1975;
p25; (s) Reynolds, G. A.; Drexhage, K. H. Opt Commun 1975, 13, 222;
(t) Snavely, B. B. In Organic Molecular Photophysics; Birks, J. B., Ed.;
Wiley: London, 1973; Vol.1, Chapter 5; (u) Gallivan, J. B. Mol Photochem
1970, 2, 191; (v) Grunhagen, H. H.; Witt, H. T. Z Naturforsch 1970, 25b,
373; (w) Shank, C. V.; Dienes, A.; Trozzolo, A. M.; Myer, J. A. Appl Phys
Lett 1970, 16, 405.
M
−1 cm−1) = 341, 405 (8490, 10370) nm. Fluorescence (DMSO): λ
(ΦF) = 503 (0.20). MS (ESI, neg): m/z (%) = 306 (21, M), 305 (100,
M − 1). Anal. calcd for C18H14N2O3 (306.32): C, 70.58; H, 4.61; N,
9.15. Found: C, 70.19; H, 4.40; N, 9.01.
2-Chloro-6-methoxy-3-phenylquinoline-4-carbonitrile (7).
A solution of 3-phenylquinoline-4-carbonitrile 6d (1.37 g, 5.00
mmol) in phosphorylchloride (6.0 mL) was heated under reflux
at 110°C for 12 h. The solution was cooled to 50°C and the
excess amount of phosphorylchloride was removed under
reduced pressure. The residue was poured onto ice/water (100
mL), filtered by suction and washed with water. The yield was
1.39 g (95%), yellowish prisms, mp 242–245°C (ethanol). IR
[4] Kramer, R. A.; Flehr, R.; Lay, M.; Kumke, M. U.; Bannwarth,
W. Helv Chim Acta 2009, 92, 1933.
[5] (a) Dannhardt, G.; Meindl, W.; Schober, B. D.; Kappe, T. Eur
J Med Chem 1991, 26, 599; (b) Stadlbauer, W.; Laschober, R; Kappe, T.
Liebigs Ann Chem 1990, 531; (c) Carissimi, M.; Grasso, I.; Grumelli, E.;
Milla, E.; Ravenna, F. Farmaco Ed Sci 1962, 17, 390; (d) Tyman, J. H. P.;
Payne, P. B. J Chem Res 2006, 691; (e) Zvilichovsky, G.; Fotadar, U. Org
Prep Proced Int 1974, 6, 5; (f) Matulenko, M. A.; Paight, E. S.; Frey, R.
R.; Gomtsyan, A.; DiDomenico, S.; Jiang, M.; Lee, C.-H.; Stewart, A.
O.; Yu, H.; Kohlhaas, K. L.; Alexander, K. M.; McGaraughty, S.; Mikusa,
J.; Marsh, K. C.; Muchmore, S. W.; Jakob, C. L.; Kowaluk, E. A.; Jarvis,
M. F.; Bhagwat, S. S. Bioorg Med Chem 2007, 15, 1586; (g) Chenevert,
R.; Desjardins, M. Can J Chem. 1994, 72, 2312; (h) Rios-Lombardia, N.;
Busto, E.; Gotor-Fernandez, V.; Gotor, V. Eur J Org Chem 2010, 484; (i)
Busto, E.; Gotor-Fernandez, V.; Montejo-Bernardo, J.; Garcia-Granda, S.;
Gotor, V. Org Lett 2007, 9, 4203.
1
(KBr): 3439 s, 2236 w (CN), 1618 m, 1561 w cm−1. H NMR
(300 MHz, DMSO-d6): δ 4.00 (s, 3 H, MeO), 7.36 (d, J = 2.7
Hz, 1 H, 5-H), 7.59 (s, 5 H, PhH), 7.68 (dd, J = 9.3 + 2.7 Hz, 1
H, 7-H), 8.11 (d, J = 9.3 Hz, 1 H, 8-H). Anal. calcd for
C17H11ClN2O (294.74): C, 69.28; H, 3.76; N, 9.50. Found: C,
69.67; H, 3.38; N, 9.12.
[6] (a) Beringer, F. M.; Forgione, P. S. Tetrahedron 1963, 19, 739;
(b) Baldoli, C.; Del Buttero, P.; Licandro, E.; Maiorana, S. Gazz Chim Ital
1988, 118, 409; (c) Hennessy, E. J.; Buchwald, S. L. Org Lett 2002, 4,
269; (d) Mino, T.; Yagishita, F.; Shibuya, M.; Kajiwara, K.; Shindo, H.;
Sakamoto, M.; Fujita, T. Synlett 2009, 2457; (e) Beare, N. A.; Hartwig,
J. F. J Org Chem 2002, 67, 541; (f) Djakovitch, L.; Kohler, K. J Organo-
met Chem 2000, 606, 101; (g) Setsune, J.; Ueda, T.; Shikata, K.;
Matsukawa, K.; Iida, T.; Kitao, T. Tetrahedron 1986, 42, 2647; (h) Setsune,
J.; Matsukawa, K.; Kitao, T. Tetrahedron Lett 1982, 23, 663; (i) Abd-El-
Aziz, A. S.; Lee, C. C.; Piorko, A.; Sutherland, R. G. Synth Commun
1988, 18, 291.
Acknowledgment. This research was supported by a PhD
scholarship from the Austrian Exchange Service/Academic
Cooperation and Mobility Unit (G.C.E.)
REFERENCES AND NOTES
[1] (a) Badgujar, N. S.; Pazicky, M.; Traar, P.; Terec, A.; Uray, G.;
Stadlbauer, W. Eur J Org Chem 2006, 2715; (b) Uray, G.; Badgujar, N. S.;
Kovácková, S.; Stadlbauer, W. J Heterocycl Chem 2008, 45, 165; (c)
Stadlbauer, W.; Avhale, A. B.; Badgujar, N. S.; Uray, G. J Heterocycl
Chem 2009, 46, 415.
[7] Stadlbauer, W.; Badawey, E.-S.; Hojas, G.; Roschger, P.;
Kappe, T. Molecules 2001, 6, 338.
[8] Hassner, A.; Stumer, C. Tetrahedron Organic Chemistry Series
Vol. 11: Organic Syntheses Based on Name Reactions and Unnamed
Reactions; Baldwin, J. E.; Magnus, P. D., Eds.; Pergamon, Elsevier Sci-
ence, Ltd.: Oxford, 1994.
[2] Avhale, A. B.; Prokopcová, H.; Šefcovicová, J.; Steinschifter,
W.; Täubl, A. E.; Uray, G.; Stadlbauer, W. Eur J Org Chem 2008, 563.
[3] (a) Piszczek, G.; Maliwal, B. P.; Gryczynski, I.; Jonathan, D.;
Lakowicz, J. R. J Fluorescence 2001, 11, 101; (b) Schiedel, M. S.; Briehn,
C. A.; Bäuerle, P. Angew Chem Int Ed 2001, 40, 4677; (c) Christie, R.
M.; Lui, C.-H. Dyes Pigm 1999, 42, 85; (d) Kido, J.; Iizumi, Y. Appl Phys
Lett 1998, 73, 2721; (e) Eggeling, C.; Widengren, J., Rigler, R.; Seidel, C.
A. M. Anal Chem 1998, 70, 2651; (f) Niko, A.; Tasch, S.; Meghdadi, F.;
Brandstätter, C.; Leising, G. J Appl Phys 1997, 82, 4177; (g) Christie, R.
M. Rev Prog Coloration 1993, 23, 1; (h) Becker, R. S.; Chakravorti, S.;
Gartner, C. A.; de Graca, M. M. J Chem Soc Faraday Trans 1993, 89,
1007; (i) Kuznetsova, N. A.; Kaliya, O. L. Russ Chem Rev 1992, 61,
683; (j) Haughland, R. P. In Handbook of Fluorescence Probes and
Research Chemicals; Larison, K., Ed.; Molecular Probes, Inc.: Eugene,
OR, 1992; (k) Ponomarev, O. A.; Vasina, E. R.; Mitina, V. G.; Sukhorukov,
A. A. Russ J Phys Chem 1990, 64, 518; (l) Raue R. In Ullmanns Encyclopedia
of Industrial Chemistry, 5th ed.; Elvers, B.; Hawkins, S.; Schulz, G., Eds.;
[9] Harwood, L. M. Aldrichim Acta 1985, 18, 25.
[10] (a) Cavalleri, B.; Bellasio, E.; Vigevani, A.; Testa, E. Farmaco
Ed Sci 1969, 24, 451; (b) Leonard, F.; Wajngurt, A.; Klein, M.; Meyer, H.
J Med Chem 1963, 6, 539; (c) SouthA., Jr.; Ouellette, R. J. J Am Chem
Soc 1968, 90, 7064; (d) Sokolova, V. N.; Magidson, O. Yu. Chem Hetero-
cycl Compd 1968, 385; Khim Geterotsikl Soedin 1968, 519.
[11] (a) Citterio, A.; Santi, R.; Fiorani, T.; Strologo, S. J Org Chem
1989, 54, 2703; (b) Schubert, H.; Zaschke, H. J Prakt Chem 1970, 312,
494; (c) de Gee, A. J.; Verhoeven, J. W.; Dirkx, I. P.; de Boer, T. J. Tet-
rahedron 1969, 25, 3407.
[12] (a) Stadlbauer, W.; Kappe, T. Monatsh Chem 1985, 116, 1005;
(b) Nishimura, H.; Nagai, Y.; Suzuki, T.; Sawayama, T. Yakugaku Zasshi
1970, 90, 818.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet