Simple synthesis of quinoxalin-2(1H)-one N-oxides from N-aryl-2- nitrosoanilines and alkylated cyanoacetic esters

Article abstract of DOI:10.1002/jhet.1947

N-Aryl-2-nitrosoanilines, available from the reaction of N-arylamines with nitroarenes, condense under alkaline conditions with alkylated derivatives of cyanoacetic esters furnishing quinoxalin-2(1H)-one N-oxides in good to excellent yields. The reaction

Full text of DOI:10.1002/jhet.1947

January 2014
Simple Synthesis of Quinoxalin-2(1H)-one N-Oxides from
N-Aryl-2-nitrosoanilines and Alkylated Cyanoacetic Esters
123
a
b
*
Magdalena Królikiewicz and Zbigniew Wróbel
aThe Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
bInstitute of Organic Chemistry, Polish Academy of Sciences ul., Kasprzaka 44, PL-01-224 Warsaw, Poland
*
E-mail: zbigniew.wrobel@icho.edu.pl
Received November 16, 2012
DOI 10.1002/jhet.1947
Published online 10 October 2013 in Wiley Online Library (wileyonlinelibrary.com).
N-Aryl-2-nitrosoanilines, available from the reaction of N-arylamines with nitroarenes, condense under
alkaline conditions with alkylated derivatives of cyanoacetic esters furnishing quinoxalin-2(1H)-one
N-oxides in good to excellent yields. The reaction involves the condensation of the carbanion with the
nitroso group leading to the nitrone intermediate, followed by intramolecular acylation of the amine
function.
J. Heterocyclic Chem., 51, 123 (2014).
INTRODUCTION
also frequently used [9] in the synthesis of their N-oxides.
A variety of these compounds were synthesized via an inter-
esting reaction of anilines with 1,2,2-trichloronitroethene
[10]. The later approach introduces the nitrone group together
with two lacking carbon atoms in the ring-forming process.
Wide range of biological activity of quinoxalinones and
their corresponding N-oxides have been reported [11].
They are known as antibacterial, antiviral, anticancer,
antifungal, antihelmintic, and insecticidal as well as
potential antiallergic agents [12]. Additionally, a number
of quinoxalinone derivatives are pharmacological agents
exhibiting antimalarial activity [13]. Therefore, new
methods of synthesis of this type of compounds, providing
collections of different entities for biological screening
purposes, are of serious interest.
In 2007, we published a simple method of synthesis of a
variety of N-aryl-2-nitrosoanilines via nucleophilic substi-
tution of hydrogen in nitroarenes with anilines that pro-
ceeded in the presence of potassium t-butoxide [1,2]. The
vicinal position of nucleophilic amino—and strongly elec-
trophilic nitroso—groups makes these compounds very
interesting starting materials for domino reactions with
properly equipped dipolar partners, leading to a variety of
heterocyclic systems. It was already shown that reactions
of title compounds with comparatively acidic sulfones
(Scheme 1, route 1) or acetates and phosphonoacetates
(Scheme 1, route 2) are efficient ways of synthesis of
benzimidazoles [3] and quinoxalin-2(1H)-ones [4]. Here,
we would like to report a new reaction of N-aryl-2-nitro-
soanilines with alkylated derivatives of cyanoacetic esters
furnishing quinoxalin-2(1H)-one-4 N-oxides in moderate
to excellent yields.
Scheme 1
Reactions of 2-nitrosoarylamines with carbon nucleo-
philes leading to quinoxalin-2(1H)-one N-oxides are men-
tioned in the literature, but the reported examples are
limited to a few intramolecular reactions of pyrimidine
derivatives, easy to synthesize via direct nitrosation of
appropriate aminopyrimidines [5]. Because carbocyclic
ortho-nitrosoanilines were not so easily available, the com-
mon synthesis of carbocyclic quinoxalin-2(1H)-one N-oxides
were based on the Tennant intramolecular condensation of
substituted ortho-nitroanilines with carbanions, in which
nitrone intermediate was formed [6]. Other synthetic
approaches applied furoxanes [7] or dioximes [8] as starting
materials. Simple oxidation of quinoxalin-2(1H)-ones was
© 2013 HeteroCorporation

124
Królikiewicz and Wróbel
Vol 51
Scheme 2
Scheme 3
RESULTS AND DISCUSSION
was the system of choice, but in some cases, K2CO3/DMF
system, despite a longer reaction time, gave better yields
of the products.
Our attempts to synthesize 3-cyanoquinoxalin-2(1H)-
ones by the reaction of N-aryl-2-nitrosoaniline with methyl
cyanoacetate, following route 2 in Scheme 1(R = H, Y =
COOMe, Z = CN) [4], failed. It led to multicomponent
intractable mixture. Unexpectedly, the situation changed
radically after the alkyl substituent was introduced into
cyanoacetic ester moiety. N-(2,6-Dimethylphenyl)-5-
chloro-2-nitrosoaniline (1a) reacted smoothly with diethyl
n-butylcyanoacetate in the presence of DBU in acetonitrile
at RT furnishing 3-butyl-7-chloro-1-(2,6-dimethylphenyl)
quinoxalin-2(1H)one 4-oxide (3a) (Scheme 2, Table 1) in
94% yield. The reaction was complete within 15 min. The
We suppose that the reaction proceeds via initial addi-
tion of the carbanion to the nitrogen of the nitroso group
followed by elimination of the cyanide anion from the
adduct 4 to form nitrone (5) (Scheme 3). Subsequent
intramolecular acylation of the amine function, probably
in deprotonated form of 5, provides quinoxalinone (3).
Formation of the nitrone moiety is probably analogous
to the known reactions of carbanions-bearing leaving
groups such as diazo [14], sulfonium [15], pyridinium
[16], sulfonyl [17], or nitro [18] with nitrosoarenes. To
our knowledge, cyano group has been reported to act in
this manner only in a few cases [19], and no one was
engaged in intramolecular formation of a heterocyclic ring.
In summary, a new simple, convenient, and general
method of synthesis of various quinoxalin-2-one N-oxides
was presented. The synthesis started from easily accessible
substrates, that is, alkyl cyanoacetic esters and 2-nitroso-N-
arylanilines that can be prepared from appropriate nitroar-
enes and anilines. Diversity of the title compounds can be
achieved by simply varying the substituents in each
reagent.
1
structure of the product was confirmed by H and 13C-
NMR as well as mass spectrum and combustion analysis.
Numerous nitrosoanilines substituted in para-position to
the nitroso group with Cl, F, Ph, and MeO reacted the same
way (Scheme 2, Table 1). Changes in N-aryl substituent in
2-nitroso-N-arylamine seems to have only small or no
impact on the reaction course. The aryl group Ar can be both
carbocyclic ring with various substituents such as alkyl,
alkoxyl, halogen, as well as heterocyclic system. Bulky
alkyl group in cyanoacetic ester moiety (i-Pr versus Et or
n-Bu) only slightly lowered the reaction rate. DBU/MeCN
Table 1
Synthesis of quinoxalin-2(1H)-one N-oxides (3) from N-aryl-2-nitrosoanilines (1).
Entry
X
Ar
R
Conditionsa
Time (min)
3
Yield (%)b
1
2
3
4
5
6
7
8
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
F
Ph
OMe
OMe
F
2,6-Me2C6H3
2,6-Me2C6H3
2,6-Me2C6H3
2-MeC6H4
2-MeC6H4
4-EtOC6H4
4-EtOC6H4
4-Py
4-Py
Ph
2,6-Me2C6H3
4-MeC6H4
4-MeC6H4
4-ClC6H4
n-Bu
Et
A
A
A
A
A
A
B
A
B
A
A
B
B
A
15
20
30
15
20
5
120
15
60
15
5
a
b
c
d
e
f
94
64
93
74
89
59
74
54
77
78
98
65
43
80
i-Pr
n-Bu
i-Pr
n-Bu
n-Bu
i-Pr
i-Pr
Et
Et
Et
i-Pr
Et
f
g
g
h
i
j
k
l
9
10
11
12
13
14
150
30c
1
aA: DBU/MeCN; B: K2CO3/DMF.
bIsolated yield.
cHours
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2014
Quinoxalin-2(1H)-one N-Oxides are Formed in the Reaction of N-Aryl-2-nitrosoanilines
125
with Carbanions of Alkylated Cyanoacetic Esters
(sept., J = 7.0 Hz, 1H), 6.56 (d, J=2.1Hz, 1H), 7.26–7.30 (m, 2H),
7.31 (dd, J = 9.0, 2.1 Hz, 1H), 7.37 (dd, J = 8.1, 6.9 Hz, 1H), 8.44
(d, J= 9.0 Hz, 1H); 13C-NMR (CDCl3): d 17,1, 17.6, 26.6, 114.3,
122.6, 124.3, 129.4, 129.7, 129.9, 132.9, 133.1, 135.8, 138.2,
147.4, 155.0; MS (70 eV, electron impact) m/z 342 (7), 327 (45),
325 (100). Anal. Calcd for C19H19N2O2Cl: C, 66.57; H, 5.59; N,
8.17. Found: C, 66.21; H, 5.57; N, 8.12.
EXPERIMENTAL
Melting points are uncorrected. 1H and 13C-NMR spectra were
recorded on a Varian-NMR-vnmrs500 (Varian, Inc., presently
Agilent Technologies, Colorado Springs, CO) (500 MHz for 1H
and 125 MHz for 13C spectra) instrument at 298 K. Chemical shifts
d are expressed in parts per million referred to TMS, and coupling
constants in Hertz. IR spectra were recorded on a FT-IR Jasco
6200 (Jasco Inc., Easton, MD) apparatus. Mass spectra (EI, 70 eV)
were obtained on an AMD 604S (AMD Analysis & Technology
AG, Germany) spectrometer. Silica gel Merck 60 (230–400 mesh)
(Merck, Darmstadt, Germany) was used for column chromatogra-
phy. Acetonitrile and DMF were dried over CaH2, distilled, and
stored over molecular sieves. N-Aryl-2-nitrosoanilines (1) were
obtained following the procedures published previously [1,2].
General procedure for the synthesis of quinoxalin-2(1H)-
one N-oxides (3)
Method A. 2-Nitroso-N-arylaniline (1) (0.5 mmol) and methyl
alkylcyanoacetate (2) (1.0 mmol) were dissolved in acetonitrile
(5 mL). DBU (2.5 mmol, 0.37 mL) was added in one portion, and
the mixture was stirred at ambient temperature for the time
specified in Table 1. After the reaction was complete, the reaction
mixture was poured into saturated water solution of ammonium
chloride (10 mL), extracted with ethyl acetate (3 Â 20 mL). The
extract was dried with anhydrous sodium sulfate, and the solvent
was removed in vacuo. The residue was separated by column
chromatography (silica gel, hexane/ethyl acetate 8:1—2:1 mixture).
Method B. 2-Nitroso-N-arylaniline (1) (0.5 mmol) and methyl
alkylcyanoacetate (2) (1.0 mmol) were dissolved in DMF (5 mL),
and potassium carbonate (5 mmol, 690 mg) was added in one
portion with stirring. The reaction mixture was then stirred
vigorously at ambient temperature for the time specified in
Table 1. After the reaction was complete, the reaction mixture
was worked up as in method A.
3-Butyl-7-chloro-1-(2-methylphenyl)quinoxalin-2(1H)-one
4-oxide (3d). This compound was obtained as violet crystals
(hexane/ethyl acetate), mp 120–122ꢀC; IR (potassium bromide):
1
1653, 1614, 1585cmÀ1; H-NMR (CDCl3): d 0.97 (t, J = 7.3 Hz,
3H), 1.43–152 (m, 2H), 1.67–177 (m, 2H), 2.06 (s, 3H), 3.13 (t,
J = 7.6Hz, 2H), 6.63 (d, J = 2.1 Hz, 1H), 7.18–7.21 (m, 1H), 7.31
(dd, J = 8.9, 2.1 Hz, 1H), 7.42–7.52 (m, 3H), 8.43 (d, J = 8.9 Hz,
1H); 13C-NMR (CDCl3): d 13.8, 17.4, 23.0, 25.6, 26.7, 115.2,
122.3, 124.3, 128.1, 128.4, 129.4, 130.2, 132.0, 133.8, 133.9,
136.1, 137.9, 144.3, 156.0; MS (70 eV, electron impact) m/z 342
(2), 327 (35), 325 (100), 300 (41), 283 (73). Anal. Calcd for
C19H19N2O2Cl: C, 66.57; H, 5.59; N, 8.17. Found: C, 66.64; H,
5.60; N, 8.14.
7-Chloro-1-(2-methylphenyl)-3-isopropylquinoxalin-2(1H)-
one 4-oxide (3e). This compound was obtained as white crystals
(hexane/ethyl acetate); mp 135–137ꢀC; IR (potassium bromide):
; d 1.45 (d,
1649, 1615, 1585 cmÀ1 1H-NMR (CDCl3):
J = 7.0 Hz, 6H), 2.06 (s, 3H), 4.12 (sept., J = 7.0 Hz, 1H), 6.61
(d, J = 2.0 Hz, 1H), 7.18–7.22 (m, 1H), 7.30 (dd, J = 9.0, 2.0,
1H), 7.42–7.52 (m, 2H), 8.43 (d, J = 9.0 Hz, 1H); 13C-NMR
(CDCl3): d 17.1, 17.1, 17.4, 26.6, 115.0, 122.5, 124.2, 128.1,
128.48, 129.6, 130.2, 132.0, 133.9, 133.9, 136.1, 137.9, 147.1,
155.6; MS (70 eV, electron impact) m/z 328 (4), 313 (31), 311
(100), 284 (16), 269 (12), 241 (14). Anal. Calcd for
C18H17N2O2Cl: C, 65.75; H, 5.21; N, 8.52. Found: C, 65.59; H,
5.23; N, 8.39.
3-Butyl-7-chloro-1-(4-ethoxylphenyl)quinoxalin-2(1H)-one
4-oxide (3f). This compound was obtained as white crystals
(hexane/ethyl acetate), mp 156ꢀC; IR (potassium bromide):
3-Butyl-7-chloro-1-(2,6-dimethylphenyl)quinoxalin-2(1H)-one
4-oxide (3a). This compound was obtained as yellow crystals
(hexane), mp 172–176ꢀC; IR (potassium bromide): 1647, 1614,
1651, 1613, 1582, 1507 cmÀ1 1H-NMR (CDCl3): d 0.96 (t,
;
1586cmÀ1; H-NMR (CDCl3): d 0.97 (t, J = 7.3 Hz, 3H), 1.42–
1
J = 7.3 Hz, 3H), 1.44–1.52 (m, 2H), 1.48 (t, J = 7.0 Hz, 3H),
1.68–1.73 9 (m, 2H), 3.08–3.12 (m, 2H), 4.13 (q, J = 7.0 Hz,
2H), 6.81 (d, J = 2.1 Hz, 1H), 7.09–7.12 (m, 2H), 7.18–7.21 (m,
2H), 7.29 (dd, J = 8.9, 2.1 Hz, 1H), 8.40 (9d, J = 8.9 Hz, 1H);
13C-NMR (CDCl3): d 13.8, 14.7, 23.1, 25. 7, 26.7, 63.9, 115.8,
116.2, 122.1, 124.1, 127.0, 129.3, 129.5, 134.7, 137.6, 144.1,
156.8, 159.8; MS (70 eV, electron impact) m/z 372 (3), 357
(37), 355 (100), 330 (34), 313 (70), 257 (22). Anal. Calcd for
C20H21N2O3Cl: C, 64.43; H, 5.68; N, 7.51. Found: C, 63.98; H,
5.65; N, 7.36.
1.51 (m, 2H), 1.69–1.73 (m, 2H), 2.01 (s, 6H), 3.13–3.16 (m,
2H), 6.58 (d, J = 2.1 Hz, 1H), 7.26–7.30 (m, 2H), 7.32 (dd,
J = 8.9, 2.1 Hz, 1H), 7.37 (dd, J = 8.1, 7.0 Hz, 1H), 8.44 (d,
J = 8.9 Hz, 1H); 13C-NMR (CDCl3): d 13.8, 17.6, 22.9, 25.5,
26.7, 114.4, 122.4, 124.4, 129.4, 129.5, 130.0, 132.9, 133.0, 135.8,
138.2, 144.5, 155.5; MS (70 eV, electron impact) m/z 356 (2), 341
(39), 339 (100), 314 (39), 297 (64). Anal. Calcd for C20H21N2O2Cl:
C, 67.32; H, 5.93; N, 7.85. Found: C, 67.71; H, 6.47; N, 8.15.
7-Chloro-1-(2,6-dimethylphenyl)-3-ethylquinoxalin-2(1H)-one
4-oxide (3b). This compound was obtained as white crystals
(hexane/ethyl acetate), mp 164–167ꢀC; IR (potassium bromide):
7-Chloro-3-isopropyl-1-pyridin-4-ylquinoxalin-2(1H)-one
4-oxide (3g). This compound was obtained as yellow crystals
(hexane/ethyl acetate), mp178–180ꢀC; IR (potassium bromide):
1
1650, 1615, 1587 cmÀ1; H-NMR (CDCl3): d 1.29 (t, J = 7.4 Hz,
1
1648, 1617, 1586cmÀ1; H-NMR (CDCl3): d 1.44 (d, J = 7.0 Hz,
3H), 2.01 (s, 3H), 3.16 (q, J = 7.4 Hz, 4H), 6.58 (d, J = 2.1 Hz,
1H), 7.28–7.30 (m, 2H), 7.33 (dd, J = 9.0, 2.1 Hz, 1H), 7.38 (dd,
J = 8.1, 7.1 Hz, 1H), 8.45 (d, J = 9.0 Hz, 1H); 13C-NMR (CDCl3):
d 9.0, 17.6, 19.4, 114.4, 122.4, 124.4, 129.4, 129.5, 130.0, 132.9,
133.0, 135.8, 138.3, 145.2, 155.2; MS (70 eV, electron impact)
m/z 330 (12), 328 (32), 313 (35), 311 (100), 283 (13), 255 (11).
Anal. Calcd for C18H17N2O2Cl: C, 65.75; H, 5.21; N, 8.52.
Found: C, 65.43; H, 5.30; N, 8.45.
3H), 4.07 (sept., J = 7.0 Hz, 1H), 6.69 (d, 2.0 Hz, 1H), 7.32–7.36
(m, 3H), 8.43 (d, J = 9.0Hz, 1H), 8.94–8.97 (m, 2H); 13C-NMR
(CDCl3): d 17.0, 26.6, 114.9, 122.7, 123.7, 124.7, 129.7, 133.1,
138.0, 142.9, 146.7.152.4, 155.5; MS (70 eV, electron impact)
m/z 315 (3), 300 (30), 298 (100). Anal. Calcd for
C19H19N2O2Cl; C, 60.86; H, 4.47; N, 13.31. Found: C, 60.85;
H, 4.36; N, 13.38.
7-Chloro-1-(2,6-dimethylphenyl)-3-isopropylquinoxalin-2(1H)-
one 4-oxide (3c). This compound was obtained as orange crystÀal1s
1H-NMR (CDCl3): d 1.46 (d, J = 7.0 Hz, 6H), 2.00 (s, 6H), 4.14
3-Ethyl-7-fluoro-1-phenylquinoxalin-2(1H)-one 4-oxide (3h).
This compound was obtained as yellow crystals, mp 158-159ꢀC;
IR (potassium bromide): 1649, 1631, 1589 cmÀ1 1H-NMR
;
(CDCl3): d 1.29 (t, J = 7.4 Hz, 3H), 3.13 (q, J = 7.4 Hz, 2H), 6.45
(hexane/ethyl acetate), mp 170–173ꢀC; 1653, 1615, 1584 cm
;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

126
Królikiewicz and Wróbel
Vol 51
(dd, JHF = 9.7 Hz, J = 2.5 Hz, 1H), 7.06 (ddd, JHF = 7.5 Hz, J = 9.3,
2.5 Hz, 1H), 7.30–7.34 (m, 2H), 7.58–7.67 (m, 3H), 8.49
(dd, JHF = 5.7 Hz, J = 9.3 Hz, 1H). 13C-NMR (CDCl3): d 9.0,
19.3, 102.8 (d, JCF = 29 Hz), 111.7 (d, JCF = 24 Hz), 123.2
(d, JCF = 10 Hz), 127.4, 128.4, 129.9, 130.5, 135.1 (d, JCF =9Hz),
144.0, 156.5, 163.9 (d, JCF = 251 Hz) (lack of one signal); MS
(70 eV, electron impact) m/z 284 (24), 267 (100), 239 (27). Anal.
Calcd for C16H13N2O2F: C, 67.60; H, 4.61; N, 9.85. Found: C,
67.91; H, 4.44; N, 9.88.
129.9, 130.8, 133.5, 134.8 (JCF = 11.5 Hz), 136.1, 143.9, 156.4,
163.9 (JCF = 251.8 Hz). MS (70eV, electron impact) m/z 318
(24), 301 (100), 273 (19). Anal. Calcd for C16H12N2O2ClF: C,
60.29; H, 3.79; N, 8.79. Found: C, 60.08; H, 3.74; N, 8.75.
REFERENCES AND NOTES
[1] Wróbel, Z.; Kwast, A. Synlett 2007, 1525.
[2] Wróbel, Z.; Kwast, A. Synthesis 2010, 3865.
[3] Wróbel, Z.; Stachowska, K.; Grudzień, K.; Kwast, A. Synlett
2011, 1439.
[4] Wróbel, Z.; Stachowska, K.; Kwast, A.; Gościk, A.; Królikie-
wicz, M.; Pawłowski, R.; Turska, I. Helv Chim Acta. 2013, 96, 956.
[5] (a) Steinlin, T.; Vasella, A. Helv. Chim. Acta 2009, 92,588; (b)
Steinlin, T.; Sonati, T.; Vasella, A. Helv Chim Acta 2008, 91, 1879; (c)
Pachter, I. J.; Nemeth, P. E.; Villani, A. J. J Org Chem 1963, 28, 1197.
[6] (a) Sakata, G.; Makino, K.; Morimoto, K. Heterocycles, 1985,
23, 143; (b) Takano, Y.; Shiga, F.; Asano, J.; Ando, N.; Uchiki, H.; Fuku-
chi, K.; Anraku, T. Bioorg Med Chem 2005, 13, 5841; (c) Takano, Y.;
Shiga, F.; Asano, J.; Ando, N.; Uchiki, H.; Anraku, T. Bioorg Med Chem
Lett 2003,13, 3521.
[7] (a) Ley, K.; Seng, F. Synthesis 1975, 415; (b) Monge, A.; Lla-
mas, A.; Pasqual, M. A. An Quim 1977, 73, 1208; Chem. Abstr. 1977, 87,
184460.
[8] (a) Duda, T. A.; Sveshnikova, L. L.; Khlestkin, V. K.; Dembo,
K. A.; Yanusova, L. G.; Rus J Phys Chem 2009, 83, 654; (b) Abushanab,
E. J Org Chem 1970, 35, 4279 (c) Abushanab, E. J Org Chem 1973, 38,
3105.
[9] (a) Toman, J.; Klicnar, J. Collect Czech Chem Commun 1984,
49, 976; (b) Cazaux, L.; Faher, M.; Picard, C.; Tisnes, P. Can J Chem
1993, 71, 2007; (c) Sakata, G.; Makino, K.; Chem Lett 1984, 323; (d)
Cazaux, L.; Faher, M.; Picard, C.; Tisnes, P.; Can J Chem 1993, 71,
2007; (e) Clark-Lewis, J. W. J Chem Soc 1957, 439.
[10] Meyer, Ch.; Zapol’sk, V. A.; Adam, A. E. W.; Kaufmann, D.
E. Synthesis 2008, 2575.
1-(2,6-Dimethylphenyl)-3-ethyl-7-phenylquinoxalin-2(1H)-
one 4-oxide (3i). This compound was obtained as yellow
crystals (hexane/ethyl acetate), mp 166–169ꢀC; IR (potassium
bromide): 1649, 1610, 1594 cmÀ1
;
1H-NMR (CDCl3): d 1.32
(t, J = 7.4 Hz, 3H), 3.21 (q, J = 7.4 Hz, 2H), 6.76 (d, J = 1.8 Hz,
1H), 7.26–7.30 (m, 2H), 7.34–7.42 (m, 7H), 7.59 (dd, J = 8.7,
1.8 Hz, 1H), 8.56 (d, J = 8.7 Hz, 1H); 13C-NMR (CDCl3): d
9.1, 17.7, 19.4, 112.7, 121.3, 123.2, 127.3, 128.6, 129.0,
129.3, 129.7, 130.2, 132.5, 133.3, 135.9, 139.0, 145.0, 145.2,
155.4; MS (70 eV, electron impact) m/z 370 (24), 353 (100),
325 (10), 297 (12). Anal. Calcd for C24H22N2O2: C, 77.81; H,
5.99; N, 7.56. Found: C, 77.49; H, 6.09; N, 7.67.
3-Ethyl-7-methoxy-1-(4-methylphenyl)quinoxalin-2(1H)-one
4-oxide (3j). This compound was obtained as white crystals
(hexane/ethyl acetate), mp 207–209ꢀC; IR (potassium bromide):
1651 cmÀ1 1H-NMR (CDCl3): d 1.28 (t, J = 7.4 Hz, 3H), 2.47
;
(s, 3H), 3.12 (q, J = 7.4 Hz, 2H), 3.72 (s, 3H), 6.20 (d,
J = 2.5 Hz, 1H), 6.89 (dd, J = 9.3, 2.5 Hz, 1H), 7.17–7.21 (m,
2H), 7.38–7.42 (m, 2H), 8.39 (d, J = 9.2 Hz, 1H); 13C-NMR
(CDCl3): d 9.1, 19.2, 21.3, 55.7, 100.2, 110.7, 122.2, 125.4,
128.2.131.0, 132.8, 135.2, 142.6, 156.9, 161.8; MS (70 eV,
electron impact) m/z 310 (20), 293 (100). Anal. Calcd for
C18H18N2O3: C, 69.66; H, 5.85; N, 9.03. Found: C, 69.62; H,
5.86; N, 9.12.
[11] (a) Awad, I.; Hassan, K. Collect Czech Chem Commun 1990,
2715; (b) Gazit, A.; App, H.; McMahon, G.; Chen, J.; Levitzki, A.; Boh-
mer, F. D. J Med Chem 1996, 39, 2170; (c) Carta, A.; Paglietti, G.; Nikoo-
kar, M. E. R.; Sanna, P.; Sechi, L.; Zanetti, S. Eur J Med Chem 2002, 37,
355; (d) Carta, A.; Loriga, M.; Zanetti, S.; Sechi, L. A. Farmaco 2003, 58,
1251.
[12] Loev, B.; Musser, J. H.; Brown, R. E.; Jones, H.; Kahen, R.;
Huang, F.-C.; Khandwala, A.; Sonnino-Goldman, P.; Leibowitz, M. J
Med Chem 1985, 28, 363.
[13] Zarranz, B.; Jaso, A.; Aldana, I.; Monge, A.; Maurel, S.;
Deharo, E.; Jullioan, V.; Sauvain, M. Drug Res 2005, 55, 754.
[14] Baldwin, J. F.; Qureshi, A. K.; Sklarz, B. J. Chem Soc 1969,
1073.
[15] (a) Hamer, J.; Macaluso, A. Chem Rev 1964, 64, 473; (b)
Johnson, A. W. J Org Chem 1963, 28, 252.
[16] (a) Nace, H. R.; Nelander, D. H. J Org Chem 1964, 29, 1677;
(b) Krohnke, F. Angew Chem Int Ed Engl 1963, 2, 380.
[17] Johnson, A. W. Chem Ind 1963, 1119.
[18] Lypkalo, I. M.; Ioffe, S. L.; Strelenko, Y.; Tartakovsky, V. A.
Russ Chem Bull 1996, 45, 856.
[19] (a) Aurich, G Chem Ber 1965, 98, 3917; (b) Makosza, M.;
Jagusztyn-Grochowska, M.; Ludwikow, M.; Jawdosiuk, M. Tetrahedron
1974, 30, 3723; (c) Jawdosiuk, M.; Ostrowska, B.; Makosza, M. J Chem
Soc D 1971, 548.
3-Isopropyl-1-(4-methylphenyl)-7-methoxyquinoxalin-2(1H)-
one 4-oxide (3k). This compound was obtained as light brown
crystals (hexane/ethyl acetate), mp 164–167ꢀC; IR (potassium
bromide): 1655 (C═O) cmÀ1 1H-NMR (CDCl3): d 1.45 (d,
;
J = 7.0 Hz, 6H), 2.64 (s, 3H), 3.71 (s, 3H), 4.11 (sept., J = 7.0,
1H), 6.17 (d, J = 2.5 Hz, 1H), 6.88 (dd, J = 9.3, 2.6 Hz, 1H),
7.17–7.21 (m, 2H), 7.39–7.42 (m, 2H), 8.38 (d, J = 9.3 Hz, 1H);
13C-NMR (CDCl3): d 17.2, 21.3, 26.4, 55.7, 100.0, 110.7,
122.4, 125.6, 128.2, 131.0, 132.9, 135.3, 139.6, 144.7, 156.8,
161.8; MS (70 eV, electron impact) m/z 324 (10), 307 (100).
Anal. Calcd for C19H20N2O3: C, 70.35; H, 6.21; N, 8.64.
Found: C, 70.45; H, 6.11; N, 8.79.
1-(4-Chlorophenyl)-3-ethyl-7-fluoroquinoxalin-2(1H)-one
4-oxide (3l). This compound was obtained as white crystals
(hexane/ethyl acetate), mp 21–218ꢀC : IR (potassium bromide):
1
1653, 1632, 1593 cmÀ1; H-NMR (CDCl3): d 1.27 (t, J = 7.4 Hz,
3H), 3.11 (q, J = 7.4 Hz, 2H), 6.46 (dd, J = 2.5 Hz, JCF = 9.5 Hz,
1H), 7.07 (ddd, J = 9.6 Hz, 2.6 Hz, JCF = 7.6 Hz, 1H), 7.26–7.30
(m, 2H), 7.60–7.63 (m, 2H), 8.48 (dd, J = 9.3 Hz, JCF = 5.6 Hz,
1H). 13C-NMR (CDCl3): d 9.0, 19.3, 102.6 (JCF = 28.8Hz),
111.9 (JCF = 23.5Hz), 123.4 (JCF = 10.4Hz), 127.5 (JCF = 2.3 Hz),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet