Efficient synthesis of 1-arylquinoxalin-2(1H)-ones via cyclocondensation of N-Aryl-substituted 2-nitrosoanilines with functionalized alkyl acetates

Article abstract of DOI:10.1002/hlca.201200304

N-Aryl-substituted 2-nitrosoanilines (=2-nitrosobenzenamines) 1, readily available by nucleophilic substitution of the ortho-H-atom in nitroarenes with arenamines, react with 2-substituted acetic acid esters in the presence of a weak base giving 1-arylquinoxalin-2(1H)-ones (Scheme 2). This cyclocondensation allows for the synthesis of compounds 2-4, unsubstituted at C(3) or substituted by alkyl, aryl, ester, amide, and keto groups, in good to excellent yields (Tables 1-4). Copyright

Full text of DOI:10.1002/hlca.201200304

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Helvetica Chimica Acta – Vol. 96 (2013)
Efficient Synthesis of 1-Arylquinoxalin-2(1H)-ones via Cyclocondensation
of N-Aryl-Substituted 2-Nitrosoanilines with Functionalized Alkyl Acetates
by Zbigniew Wro´bel*, Karolina Stachowska, Andrzej Kwast, Agata Gos´cik1),
Magdalena Kro´likiewicz2), Robert Pawłowski2), and Izabela Turska3)
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44, PL-01-224 Warszawa
(phone: þ 48226328395; fax: þ 48226326681; e-mail: zbigniew.wrobel@icho.edu.pl)
N-Aryl-substituted 2-nitrosoanilines (¼2-nitrosobenzenamines) 1, readily available by nucleophilic
substitution of the ortho-H-atom in nitroarenes with arenamines, react with 2-substituted acetic acid
esters in the presence of a weak base giving 1-arylquinoxalin-2(1H)-ones (Scheme 2). This cyclo-
condensation allows for the synthesis of compounds 2 – 4, unsubstituted at C(3) or substituted by alkyl,
aryl, ester, amide, and keto groups, in good to excellent yields (Tables 1 – 4).
Introduction. – Nucleophilic substitution of a H-atom in aromatic nitro compounds
is a reaction of great value in organic synthesis because it allows to introduce a variety
of substituents into electron-deficient aromatic rings without the requirement for the
presence of a leaving group [1]. As the most versatile leaving groups in the classical
SNAr processes are halogen atoms, the alternative substitution of a H-atom (SNHAr)
provides a shorter, halogen-free, thus more environmentally friendly synthetic
approach. A few years ago, we described a synthesis of a wide range of N-aryl-
substituted 2-nitrosoarenamines via nucleophilic substitution of a H-atom in the
reaction of nitroarenes with anilines (¼ benzenamines) in the presence of a strong base
[2]. The reaction belongs to a narrow, but interesting group of SNHAr processes, in
which sH-adducts are converted into substituted nitrosoarenes according to an
intramolecular redox stoichiometry [3]. It should be stressed that such reactions
proceed also with o- and p-halonitrobenzenes; thus a general rule that nucleophilic
substitution of H-atom proceeds faster than conventional substitution (SNAr) of
halogen atoms is confirmed [1c][4]. The reaction is so far the only useful method for
the preparation of N-aryl-substituted 2-nitrosoanilines (¼2-nitrosobenzenamines) and
now, a variety of them become readily available.
N-Aryl-substituted 2-nitrosoanilines are ideal starting materials for the regioselec-
tive synthesis of many polycyclic compounds because they provide an aromatic ring
having two N-containing groups of opposite reactivity, a nucleophilic amino group and
a strongly electrophilic nitroso group. In our preceding papers, we reported simple and
efficient synthesis of substituted phenazines [5] and benzimidazoles [6], which benefit
1
)
Summer 2011 trainee from the Interfaculty Department of Biotechnology, Warsaw University of
Life Sciences, Warsaw.
Summer 2011 trainee from the Faculty of Chemistry, University of Warsaw, Warsaw.
Summer 2010 trainee from the Faculty of Chemistry, Warsaw University of Technology, Warsaw.
2
3
)
)
ꢀ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

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957
from that feature. Here, we report the synthesis of 1-arylquinoxalin-2(1H)-ones in the
reaction between N-aryl-substituted 2-nitrosoanilines and 2-substituted acetic acid
esters.
The quinoxalin-2(1H)-one scaffold is a core of an important class of heterocyclic
molecules, which has shown a variety of biological activities such as antithrombotic,
antitumor, antimicrobial, and many other activities [7 – 11]. The 1-arylquinoxalin-
2(1H)-ones, although less common than their 1-alkyl and unsubstituted analogues,
draw also notable attention as interesting biologically active compounds [12].
Almost all known synthetic ways to quinoxalinones can be derived from ortho-
halonitroarenes as a source of the carbocyclic ring of the quinoxalin-2(1H)-ones and of
at least one of its N-atoms (Scheme 1). The classical and most common approach
consists in the coupling of substituted ortho-arenediamines with appropriate a-keto
acid derivatives (Scheme 1, Path a). This method is widely applied for unsubstituted, 1-
alkyl or 1-aryl derivatives and is quite practical in numerous instances [7][10][13].
However, it reveals some limitations concerning location of substituents which led to
mixtures of isomers [7c]. Differentiation of the two ortho N-containing groups with
respect to their reactivity could solve the regioselectivity issues but is usually much
more laborious (Scheme 1, Path c) [11b][14].
Scheme 1. Common Existing Synthetic Ways to Substituted Quinoxalin-2(1H)-ones
Aromatic ortho-diamines require often multistep synthesis via substitution of the
halogen atom in ortho-halonitrobenzene derivatives with an appropriate amine,
followed by reduction of the nitro group. The synthesis of the suitable dicarbonyl or an
equivalent partner can also be challenging (Scheme 1, Path b) [10b].
Usually, 1-aryl-substituted quinoxalin-2(1H)-ones were obtained by standard
condensations of N-arylarenamines [15] (Scheme 1, Path a and b); thus, preceding
synthesis of the latter from the appropriate 2-fluoronitroarenes was often required.
Sporadically, other reactions leading to 1-arylquinoxalin-2(1H)-ones were also
reported [16]. Recently, Chen and Bao developed a regioselective, one-pot, CuI
catalyzed reaction of N-(2-iodophenyl)methanesulfonamides with N-aryl-2-haloacet-

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Helvetica Chimica Acta – Vol. 96 (2013)
amides, leading directly to quinoxalin-2(1H)-ones with 1-aryl and 1-alkyl substituents
in good yields (Scheme 1, Path d) [17].
The simplest approach to substituted quinoxalinones appears to be the use of 2-
nitrosoanilines which seem to be supreme substrates for the formation of the fused
pyrazinone moiety. Since the N-containing groups in the substrate are of opposite
reactivity, formation of the new CꢀN bonds in the reaction with suitable bifunctional
reagents should occur regiospecifically. For instance, formation of the pyrazinone ring
in the reaction of enolates of malonates and b-keto acetates, etc., with nitroso
derivatives of pyrimidinamines [18] or aminouracils [19] was used for the synthesis of
some substituted pteridinones.
Results and Discussion. – In this study, we show that N-aryl-substituted 2-
nitrosoanilines 1 undergo base-promoted cyclocondensation with esters of acetic acid
activated by carbanion-stabilizing substituents, providing a variety of 1-arylquinoxalin-
2(1H)-ones in good to excellent yields (Scheme 2). The reaction occurs under very mild
conditions and, when combined with the earlier described general procedure for the
preparation of substituted N-aryl-substituted 2-nitrosoanilines 1, provides the shortest,
two-step method for the synthesis of compounds 2 – 4 from simple, easily available
nitroarenes (Scheme 2).
Scheme 2. Synthesis of Substituted 1-Arylquinoxalin-2(1H)-ones 2 – 4 from Nitroarenes. For R1 to R5,
Ar1 and Ar2, see Tables 1 (2), 2 (3), and 3 and 4 (4)
N-Aryl-substituted 2-nitrosoanilines are highly NꢀH acidic compounds and, to
behave as electrophilic reagents in the condensation with enolates, they should remain
neutral, at least partially, while the nucleophile precursor is, at least partially,
deprotonated. Thus, only such alkyl acetates that contain an additional electron-
withdrawing group meet this requirement. The reaction of 1 with esters of acetic acid

Helvetica Chimica Acta – Vol. 96 (2013)
959
substituted by carbonyl groups occurred by simple mixing of both reactants in the
presence of an excess of a weak base at room temperature. Suitable selection of the
esters allowed for synthesis of 1-arylquinoxalin-2(1H)-ones 2 – 4 with a number of
substituents at C(3) including alkoxycarbonyl, benzoyl, amido or aryl substituents. For
strongly CꢀH acidic esters, such as alkyl malonates, the heterogeneous system K2CO3 in
MeCN worked well ( ! 2; Table 1). Less acidic 2-arylacetates required more basic
conditions, thus Cs2CO3 in MeCN or DBU in DMF (DBU ¼ 1,8-diazabicyclo[5.4.0]un-
dec-7-ene) were effective for the synthesis of quinoxalin-2(1H)-ones containing a wide
range of carbo- and heterocyclic substituents at C(3) ( ! 3; Table 2).
Table 1. Cyclocondensation of N-Aryl-Substituted 2-Nitrosoanilines 1 with Carbonyl-substituted Acetic
Acid Estersa). See Scheme 2, Path a.
Entry R1
R2
Ar1
R3
R4
Time [h] Product 2 Yieldb) [%]
1
2
3
4
5
6
7
8
9
H
Cl
Cl
Cl
2,6-Me2C6H3 MeO MeO
1
a
b
c
d
e
f
g
h
i
93
82
68
91
88
76
93
93
93
83
4-EtOC6H4
4-EtOC6H4
MeO MeO
MeO MeO
MeO MeO
2.5
0.5
1c)
1
2
24
MeO Cl
H
H
H
H
H
Cl
H
MeO 4-MeC6H4
Ph
Cl
Cl
Cl
Cl
2,6-Me2C6H3 MeO MeO
4-EtOC6H4
pyridin-4-yl
Ph
MeO MeO
MeO MeO
MeO MeO
1.5
1
4-ClC6H4
EtO
EtO
Ph
10
MeO 4-MeC6H4
N(C2H4)2O 72
j
a) Conditions: K2CO3 in MeCN, r.t. b) Yield of isolated product. c) Reaction carried out in DMF.
Table 2. Synthesis of 3-Arylquinoxalin-2(1H)-ones 3 from N-Aryl-Substituted 2-Nitrosoanilines 1 and 2-
Arylacetic Acid Esters. See Scheme 2, Path b.
Entry R1
R2
Ar1
Ar2
R3
Conditiona), Product 3 Yieldb)
Time [h]
[%]
1
2
3
4
5
6
7
8
9
H
H
Cl
Cl
2,6-Me2C6H3 Ph
2,6-Me2C6H3 Ph
4-EtOC6H4 Ph
MeO
(i-Pr)2N A, 96
MeO
MeO
EtO
A, 1
a
a
b
c
d
e
f
g
h
i
74
54
75
80
98
97
78
64
82
62
67
MeO Cl
H
B, 2
MeO 4-MeC6H4
Ph
C, 24
C, 0.2
C, 0.02
A, 1
A, 24
A, 20
A, 20
A, 20
H
H
H
H
H
MeO 4-MeC6H4
MeO 4-MeC6H4
Cl
MeO 4-MeC6H4
MeO 4-MeC6H4
2-thienyl
pyridin-4-yl
EtO
2,6-Me2C6H3 6-MeO(3-NO2)pyridin-2-yl EtO
6-MeO(3-NO2)pyridin-2-yl EtO
1-nitronaphthalen-2-yl
4-EtOC6H4 5-Cl(2-NO2)C6H3
EtO
EtO
EtO
10
11
MeO Cl
H
MeO 4-MeC6H4
5-Cl(2-NO2)C6H3
j
a) Base and solvent: A ¼ DBU in MeCN, B ¼ Cs2CO3 in DMFand, C ¼ DBU in DMF. b) Yield of isolated
product.
Attempts to obtain 3-alkyl-substituted quinoxalinones in the reaction of 1 with
esters of alkanoic acids failed, apparently due to the unfavorable relation of the acidity
of the reagents. More basic alkanolates or other stronger bases in protic solvents had to

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be excluded owing to a predisposition of N-aryl-substituted 2-nitrosoanilines to
intramolecular cyclization leading to phenazines under such conditions [5].
To overcome this limitation, we tried to use acetic acid derivatives activated by
substituents capable to depart in the course of the condensation. Since the initial
attempts with the Wittig reagents were unsuccessful, we switched to the more reactive
carbanions of ethyl 2-(diethoxyphosphoryl)acetate, -propanonate and -butanoate. The
reactions of 1 with these reagents, carried out in the presence of LiCl/DBU in MeCN,
gave 3-alkyl- or 3-unsubstituted quinoxalin-2(1H)-ones 4 in moderate to good yields,
with a few exceptions in which the yield was rather low (Table 3). For the synthesis of
3-unsubstituted 1-arylquinoxalin-2(1H)-ones 4a – 4c, an alternative two-step procedure
was carried out (Scheme 2, Path a þ d). It consisted of the reaction of 1 with dimethyl
malonate resulting in 2 (Table 1), followed by hydrolysis/decarboxylation of the 3-
methoxycarbonyl group (Table 4). The latter reaction proceeded relatively easily, did
not require copper or other catalysts, and occurred efficiently at 150 – 1808 in sulfolane
(¼tetrahydrothiophene 1,1-dioxide). As a result, the sequence was more effective than
Table 3. Cyclocondensation of N-Aryl-Substituted 2-Nitrosoanilines 1 with Ethyl 2-(Diethoxyphosphor-
yl)acetatesa). See Scheme 2, Path c.
Entry
R1
R2
Ar1
R5
Product 4
Time [h]
Yieldb) [%]
1
2
3
4
5
6
7
8
9
H
Cl
H
MeO
MeO
H
H
H
Cl
Cl
Cl
Cl
Cl
Cl
MeO
Ph
Ph
2,6-Me2C6H3
4-EtOC6H4
4-ClC6H4
4-EtOC6H4
4-EtOC6H4
2,6-Me2C6H3
4-MeC6H4
2,6-Me2C6H3
2,6-Me2C6H3
4-EtOC6H4
4-MeC6H4
H
H
H
H
Et
Et
Et
Et
H
Me
H
Me
a
b
c
d
e
f
g
h
i
2
24
24
2.5
20
16
20
5
6
3
20
3
43
25
24
83
51
42
77
38
c
H
MeO
H
54
49
54
58
)
10
11
12
Cl
MeO
MeO
j
k
l
H
4-MeC6H4
b
c
a) Conditions: DBU/LiCl in DMF, r.t. ) Yield of isolated product. ) Accompanied by 20% of N3-(2,6-
dimethylphenyl)[1,1’-biphenyl]-3,4-diamine (5).
Table 4. Hydrolysis/Decarboxylation of Methyl 3,4-Dihydro-3-oxoquinoxaline-2-carboxylates 2 (R4 ¼
MeO)a). See Scheme 2, Path d.
Entry
R1
R2
Ar1
R5
Product 4
Yieldb)
Combined yieldb)
[%] of 2 ! 4
[%] of 1 ! 2 ! 4
1
2
3
4
5
H
Cl
H
H
H
Cl
Cl
Cl
Cl
Cl
2,6-Me2C6H3
4-EtOC6H4
4-ClC6H4
pyridin-4-yl
Ph
H
H
H
H
H
a
b
c
m
n
79
66
80
72
80
73
54
72c)
51
74
c
a) Conditions: conc. HCl soln., sulfolane, 150 – 1808. b) Yield of isolated product. ) For the preparation
of starting methyl 6-chloro-4-(4-chlorophenyl)-3,4-dihydro-3-oxoquinoxaline-2-carboxylate, see [2a].

Helvetica Chimica Acta – Vol. 96 (2013)
961
the one-step reaction of 1 with ethyl 2-(diethoxyphosphoryl)acetate (cf. Table 3,
Entries 1 – 3).
All presented cyclocondensations of 1 involve both condensation of the anion of
the ester with the nitroso group and acylation of the N-atom of the arylamino function.
The order of these events has not been considered in the literature dealing with similar
cyclization processes. Our initial belief was priority of the EhrlichꢀSachs or aza-
HornerꢀWadsworthꢀEmmons condensation followed by the intramolecular acylation,
but this sequence is not obvious. Since the acidity of the 2-nitrosoanilines 1 is not known
and rather difficult to estimate, deprotonation of the amino group and its acylation with
the neutral ester in the first step of the reaction could not be excluded. However,
attempts to acylate 1 with diethyl 2,2-dimethylmalonate, which is unable to form a
carbanion and, therefore, to react with the nitroso group, were unsuccessful. Under
typical reaction conditions, the only process was slow decomposition, no traces of the
acylation product were detected. Furthermore, formation of N3-(2,6-dimethylphen-
yl)[1,1’-biphenyl]-3,4-diamine (5), besides the expected 1-arylquinoxalin-2(1H)-one 4i,
in one of the reactions (Table 3, Entry 9) is also informative. Compound 5 was
apparently formed by hydrolysis of the primary product of the condensation, imine 6,
during the aqueous workup of the reaction mixture (Scheme 3). The above
observations corroborate the priority of the enolate reaction with the nitroso group,
although attempts to observe intermediate imines 6 in other reactions failed, which
means that the intramolecular acylation is relatively fast, even when the N,N-
diisopropylamide function is involved (Table 2, Entry 2). Thus, addition of the anionic
nucleophile to the nitroso group seems to be the first step of the reaction. Whether the
condensation is finalized with formation of the C¼N bond prior to the cyclization, or
elimination of the leaving group occurs as a final step of the quinoxalinone formation,
can not be easily determined.
Scheme 3. Possible Ways of the Formation of Quinoxalinones 2, 3, 4, and Diamine 5
Conclusions. – The presented reaction allows for the synthesis of numerous 1-
arylquinoxalin-2(1H)-ones with various substituents at C(3). Starting 2-nitrosoanilines
have become easily available via a one-step nucleophilic substitution of H-atom in

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Helvetica Chimica Acta – Vol. 96 (2013)
nitroarenes with arenamines, hence overcoming the classical halogen-substitution/
reduction sequence. The presented method is superior to the known ones also because
of its simple procedure, mild conditions and environmentally friendly character.
Combining the synthesis of N-aryl-substituted 2-nitrosoarenamines with their reaction
with active methylene groups of acetic ester derivatives, we have developed a short,
convenient way to interesting heterocyclic compounds of potential value.
Experimental Part
General. Known N-aryl-2-nitrosobenzenamines 1 were obtained following procedures published
previously [2]. Ethyl (5-chloro-2-nitrophenyl)acetate [20], methyl (6-methoxy-3-nitropyridin-2-yl)ace-
tate [21], and methyl (1-nitronaphthalen-2-yl)acetate [20] were obtained according to the literature. All
remaining reagents were commercially available. DMF and MeCN were dried (CaH2), distilled, and
stored over molecular sieves. Column chromatography (CC): silica gel (SiO2 60, 230 – 400 mesh; Merck).
M.p.: uncorrected. 1H- and 13C-NMR Spectra: Bruker-Avance-500 (500 (1H) and 125 MHz (13C)) or
Varian-NMR-vnmrs600 (600 (1H) and 150 MHz (13C)) instrument at 298 K; d in ppm rel. to Me4Si as
internal standard, J in Hz. EI-MS (70 eV): AMD-604 spectrometer; in m/z (rel. %).
New N-Aryl-2-nitrosobenzamines 1. General Procedure. To a cooled soln. of t-BuOK (6 mmol,
672 mg) in DMF (12 ml) were added dropwise at ꢀ 608 the appropriate benzenamine (2 mmol) in DMF
(2 ml) and then the nitroarene (2 mmol) in DMF (2 ml). The mixture was stirred at ꢀ608 for 30 min,
then poured into conc. NH4Cl soln. (ca. 50 ml), and extracted with AcOEt. The extract was washed
thoroughly with H2O and brine, dried (Na2SO4) and concentrated and the crude product subjected to CC
(SiO2, hexane/AcOEt or hexane/toluene).
5-Chloro-2-nitroso-N-phenylbenzenamine (1; R1 ¼ H, R2 ¼ Cl, Ar1 ¼ Ph): Yield 68%. Dark solid.
M.p. 100 – 1028. 1H-NMR (500 MHz, (D6)DMSO): 6.88 (dd, J ¼ 8.8, 1.8, 1 H); 7.17 (d, J ¼ 1.8, 1 H); 7.28 –
7.33 (m, 1 H); 7.43 – 7.51 (m, 4 H); 7.68 (br. s, 1 H); 11.49 (br. s, 1 H). 13C-NMR (125 MHz, (D6)DMSO):
115.1; 117.7; 124.5; 125.9; 126.9; 129.6; 137.6; 140.8; 143.9; 155.5. EI-MS: 231 ([M ꢀ 1]þ, 13), 215 (100),
201 (23), 166 (16). HR-MS: 232.0392 ([M ꢀ 1]þ, C12H835ClN2Oþ; calc. 232.0403).
N-(5-Chloro-2-nitrosophenyl)pyridin-4-amine (1; R1 ¼ H, R2 ¼ Cl, Ar1 ¼ pyridin-4-yl): Yield 85%.
Orange solid. M.p. 128 – 1328. 1H-NMR (500 MHz, (D6)DMSO): 6.80 (d, J ¼ 8.9, 1 H); 6.99 (dd, J ¼ 8.9,
2.0, 1 H); 7.43 – 7.46 (m, 2 H); 7.77 (d, J ¼ 2.0, 1 H); 8.48 – 8.51 (m, 2 H); 11.11 (br. s, 1 H). 13C-NMR
(125 MHz, CDCl3)4): 115.1; 116.2; 120.6; 145.0; 145.4; 151.4; 155.2. EI-MS: 233 (6, Mþ), 216 (100), 202
(11), 168 (17). HR-MS (ESI) 234.0438 ([M þ H]þ, C11H935ClþN3O; calc. 234.0429).
N-(2,6-Dimethylphenyl)-4-nitroso[1,1’-biphenyl]-3-amine (1; R1 ¼ H, R2 ¼ Ph, Ar1 ¼ 2,6-Me2C6H3).
Yield 33%. Dark solid. M.p. 117 – 1208. 1H-NMR (500 MHz, CDCl3): 2.15 (s, 6 H); 6.48 (d, J ¼ 1.6, 1 H);
7.14 – 7.24 (m, 4 H); 7.38 – 7.41 (m, 3 H); 7.46 – 7.49 (m, 2 H); 8.87 (br. s, 1 H); 12.05 (br. s, 1 H). 13C-NMR
(125 MHz, CDCl3)4): 18.2; 112.5; 117.0; 127.4; 127.8; 128.7; 128.9; 129.2; 133.7; 135.9; 139.4; 140.9; 150.4;
155.6. EI-MS: 302 (3, Mþ), 287 (100), 270 (8). HR-MS: 302.1424 (C20H18N2Oþ; calc. 302.1420).
Reaction of N-Aryl-2-nitrosobenzenamines 1 with Esters of Carbonyl- or Aryl-Activated Acetic Acid
to Quinoxalinones 2 and 3: General Procedure. To a soln. of 1 (0.5 mmol) and an appropriate ester
(0.7 mmol) in dry MeCN or DMF (6 ml) was added K2CO3 (552 mg, 4 mmol), or Cs2CO3 (1300 mg,
4 mmol), or DBU ((0.3 ml, 2.0 mmol). The mixture was stirred at r.t. for the time specified in Tables 1
and 2. Then, the mixture was poured into NH4Cl soln. and extracted with AcOEt, the combined extract
washed with H2O and brine, dried (Na2SO4), and concentrated, and product 2 or 3 isolated by CC (SiO2).
Reaction of N-Aryl-2-nitrosobenzenamines 1 with Esters of 2-(Diethoxyphosphoryl)acetic Acid to
Quinoxalinones 4: General Procedure. To a soln. of 1 (0.4 mmol) and an appropriate 2-(diethoxyphos-
phoryl)acetic acid ester (¼2-(diethoxyphosphinyl)acetic acid ester; 0.44 mmol) in dry MeCN (5 ml)
were added LiCl (20 mg, 0.48 mmol) and DBU (0.3 ml, 2.0 mmol). The mixture was stirred at r.t. for the
time specified in Table 3. Then, the mixture was poured into NH4Cl soln. and extracted with AcOEt, the
4
)
One or more signals are not visible.

Helvetica Chimica Acta – Vol. 96 (2013)
963
combined extract washed with H2O and brine, dried (Na2SO4), and concentrated, and the product 4
isolated by CC (SiO2).
Hydrolysis/Decarboxylation of Methyl 3,4-Dihydro-3-oxoquinoxaline-3-carboxylates 2 (R4 ¼ MeO):
General Procedure. To a soln. of 2 (R4 ¼ MeO; 0.3 mmol) in sulfolane (3 ml) at r.t. was added conc. HCl
soln. (0.1 ml), and the soln. was warmed to 808 and kept at 808 until the substrate disappeared (TLC
monitoring). Then, the temp. was raised slowly to 150 – 1808, depending on the particular substrate. After
the evolution of CO2 ceased, the mixture was cooled, poured onto ice/H2O containing sat. aq. NaCl soln.
(10 ml), and extracted with AcOEt (3 ꢁ 20 ml). The combined extract was washed twice with dil. NaCl
soln., dried (Na2SO4), and concentrated, the residue subjected to CC (SiO2), and the product 4
recrystallized.
Methyl 6-Chloro-4-(2,6-dimethylphenyl)-3,4-dihydro-3-oxoquinoxaline-2-carboxylate (2a): White
crystals. M.p. 173 – 1768 (AcOEt). 1H-NMR (600 MHz, CDCl3): 1.99 (s, 6 H); 4.03 (s, 3 H); 6.54 (d,
J ¼ 2.1, 1 H); 9.26 – 7.29 (m, 2 H); 7.35 (dd, J ¼ 8.7, 2.1, 1 H); 7.35 – 7.39 (m, 1 H); 7.94 (d, J ¼ 8.7, 1 H).
13C-NMR (150 MHz, CDCl3): 17.6; 53.3; 114.3; 125.2; 129.4; 130.0; 130.5; 132.2; 132.6; 134.7; 135.3;
139.2; 149.2; 150.9; 163.6. EI-MS: 342 (94, Mþ), 282 (100), 255 (61), 219 (87). HR-MS: 342.0777
(C18H1535ClN2Oþ3 ; calc. 342.0771).
Methyl 6,8-Dichloro-4-(4-ethoxyphenyl)-3,4-dihydro-3-oxoquinoxaline-2-carboxylate (2b): Yellow
crystals. M.p. 203 – 2058 (hexane/AcOEt). 1H-NMR (600 MHz, CDCl3): 1.48 (t, J ¼ 7.0, 3 H); 4.02 (s,
3 H); 4.12 (q, J ¼ 7.0, 2 H); 6.67 (d, J ¼ 2.2, 1 H); 7.08 – 7.12 (m, 2 H); 7.13 – 7.16 (m, 2 H); 7.43 (d, J ¼ 2.2,
1 H). 13C-NMR (150 MHz, CDCl3): 14.7; 53.3; 63.9; 114.6; 116.2; 125.4; 126.4; 127.4; 128.9; 136.6; 137.4;
138.0; 149.5; 152.0; 150.0; 163.4. EI-MS: 394 (81), 392 (100, Mþ), 305 (33), 278 (64). HR-MS: 392.0323
(C18H1435Cl2N2Oþ4 ; calc. 392.0331).
Methyl 6-Chloro-4-(4-ethoxyphenyl)-3,4-dihydro-8-methoxy-3-oxoquinoxaline-2-carboxylate (2c).
1
Pale yellow crystals. M.p. 258 – 2608 (AcOEt). H-NMR (400 MHz, CDCl3): 1.47 (t, J ¼ 7.0, 3 H); 3.99
(s, 3 H); 4.04 (s, 3 H); 4.11 (q, J ¼ 7.0, 2 H); 6.33 (d, J ¼ 2.0, 1 H); 6.78 (d, J ¼ 2.0, 1 H); 7.07 – 7.11 (m,
2 H); 7.14 – 7.18 (m, 2 H). 13C-NMR (100 MHz, CDCl3): 14.7; 53.1; 56.9; 63.9; 106.6; 107.9; 116.1; 121.3;
127.0; 129.0; 137.5; 139.6; 146.4; 152.5; 157.2; 159.8; 163.5. EI-MS: 388 (100, Mþ), 356 (42), 328 (29), 300
(92), 272 (49). HR-MS: 388.0834 (C19H1735ClN2O5þ ; calc. 388.0826).
Methyl 3,4-Dihydro-6-methoxy-4-(4-methylphenyl)-3-oxoquinoxaline-2-carboxylate (2d). Pale green
crystals. M.p. 1578 (hexane/AcOEt). 1H-NMR (500 MHz, (D6)DMSO): 2.44 (s, 3 H); 3.69 (s, 3 H); 3.89
(s, 3 H); 5.95 (d, J ¼ 2.6, 1 H); 7.07 (dd, J ¼ 9.0, 2.6, 1 H); 7.30 – 7.34 (m, 2 H); 7.43 (m, 2 H); 7.87 (d, J ¼
9.0, 1 H). 13C-NMR (125 MHz, (D6)DMSO): 21.3; 53.0; 56.2; 99.7; 112.2; 126.6; 128.4; 131.1; 132.2;
133.0; 137.4; 139.6; 146.0; 152.4; 162.7; 164.4. EI-MS: 324 (100, Mþ), 293 (10), 281 (16), 237 (47). HR-
MS: 324.1117 (C18H16N2Oþ4 ; calc. 324.1110).
Methyl 4-(2,6-Dimethylphenyl)-3,4-dihydro-3-oxo-6-phenylquinoxaline-2-carboxylate (2e): Yellow
1
crystals. M.p. 1588 (hexane/ AcOEt). H-NMR (500 MHz, CDCl3): 2.02 (s, 6 H); 4.04 (s, 3 H); 6.13 (d,
J ¼ 2.0, 1 H); 7.26 – 7.28 (m, 2 H); 7.34 – 7.44 (m, 6 H); 7.62 (dd, J ¼ 8.4, 2.0, 1 H); 8.09 (d, J ¼ 8.4, 1 H).
13C-NMR (125 MHz, CDCl3): 17.7; 53.2; 112.4; 123.8; 127.4; 128.7; 129.0; 129.3; 129.8; 131.4; 131.5; 133.0;
134.2; 135.4; 139.2; 146.0; 148.7; 151.4; 163.9. EI-MS: 384 (100, Mþ), 324 (62), 297 (60). HR-MS:
384.1484 (C24H20N2Oþ3 ; calc. 384.1474).
Methyl 6-Chloro-4-(4-ethoxyphenyl)-3,4-dihydro-3-oxoquinoxaline-2-carboxylate (2f): Yellow solid.
M.p. 181 – 1828. 1H-NMR (600 MHz, CDCl3): 1.48 (t, J ¼ 7.0, 3 H); 4.02 (s, 3 H); 4.13 (q, J ¼ 7.0, 2 H); 6.76
(d, J ¼ 2.1, 1 H); 7.09 – 7.12 (m, 2 H); 7.16 – 7.19 (m, 2 H); 7.31 (dd, J ¼ 8.6, 2.1, 1 H); 7.89 (d, J ¼ 8.6, 1 H).
13C-NMR (150 MHz, CDCl3): 14.7; 53.2; 63.9; 115.6; 116.2; 124.9; 126.6; 129.0; 130.3; 131.9; 136.3; 138.6;
149.1; 152.3; 159.9; 163.7. EI-MS: 358 (100, Mþ), 271 (22), 243 (32). HR-MS: 358.0730 (C18H1535ClN2Oþ4 ;
calc. 358.0720).
Methyl 6-Chloro-3,4-dihydro-3-oxo-4-(pyridin-4-yl)quinoxaline-2-carboxylate (2g): Yellow solid.
M.p. 186 – 1898. 1H-NMR (500 MHz, CDCl3): 4.03 (s, 3 H); 6.68 (d, J ¼ 2.0, 1 H); 7.31 – 7.33 (m, 2 H); 7.38
(dd, J ¼ 8.6, 2.0, 1 H); 7.94 (d, J ¼ 8.6, 1 H); 8.94 – 8.97 (m, 2 H). 13C-NMR (125 MHz, CDCl3): 53.4;
114.8; 123.1; 125.5; 130.1; 132.3; 134.4; 139.1; 142.4; 148.7; 151.1; 152.4; 163.1. EI-MS: 315 (91, Mþ), 256
(23), 228 (100). HR-MS: 315.0408 (C15H1035ClN3O3þ ; calc. 315.0411).
Methyl 6-Chloro-3,4-dihydro-3-oxo-4-phenylquinoxaline-2-carboxylate (2h): Pale yellow solid. M.p.
1
184 – 1868. H-NMR (500 MHz, (D6)DMSO): 3.92 (s, 3 H); 6.49 (d, J ¼ 2.3, 1 H); 7.46 – 7.51 (m, 3 H);

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Helvetica Chimica Acta – Vol. 96 (2013)
7.60 – 7.64 (m, 1 H); 7.65 – 7.69 (m, 2 H); 7.96 (d, J ¼ 8.6, 1 H). 13C-NMR (125 MHz, (D6)DMSO): 53.3;
115.2; 124.7; 128.8; 130.3; 130.4; 130.8; 132.1; 135.2; 136.6; 137.0; 150.2; 151.9; 164.0. EI-MS: 314 (71,
Mþ), 227 (100). HR-MS: 314.0447 (C16H1135ClN2Oþ3 ; calc. 314.0458).
3-Benzoyl-5,7-dichloro-1-(4-chlorophenyl)quinoxalin-2(1H)-one (2i): Yellow crystals. M.p. 223 –
1
2258 (MeOH). H-NMR (500 MHz, CDCl3): 6.65 (d, J ¼ 2.1, 1 H); 7.25 – 7.28 (m, 2 H); 7.47 (d, J ¼ 2.1,
1 H); 7.49 – 7.53 (m, 2 H); 7.59 – 7.62 (m, 2 H); 7.62 – 7.67 (m, 1 H); 8.04 – 8.07 (m, 2 H). 13C-NMR
(125 MHz, CDCl3): 114.1; 125.6; 127.5; 128.7; 129.5; 130.2; 130.9; 132.7; 134.4; 134.5; 136.4; 136.5; 136.8;
137.7; 152.2; 154.7; 190.2. EI-MS: 430 (18, [M þ 2]þ), 428 (19, Mþ), 373 (5), 105 (100), 77 (43). HR-MS:
427.9885 (C21H1135Cl3N2Oþ2 ; calc. 427.9886).
7-Methoxy-1-(4-methylphenyl)-3-(morpholin-4-ylcarbonyl)quinoxalin-2(1H)-one (2j): White crys-
1
tals. M.p. 199 – 2028 (hexane/AcOEt). H-NMR (500 MHz, CDCl3): 2.46 (s, 3 H); 3.44 – 3.48 (m, 2 H);
3.72 (s, 3 H); 3.73 – 3.75 (m, 2 H); 3.78 – 3.85 (m, 4 H); 6.17 (d, J ¼ 2.6, 1 H); 6.92 (dd, J ¼ 9.0, 2.6, 1 H);
7.15 – 7.18 (m, 2 H); 7.39 – 7.42 (m, 2 H); 7.83 (d, J ¼ 9.0, 1 H). 13C-NMR (125 MHz, CDCl3): 21.3; 42.1;
47.0; 55.7; 66.6; 66.7; 99.6; 111.8; 127.3; 127.6; 131.0; 131.7; 132.3; 136.3; 139.9; 149.9; 152.9; 162.0; 164.1.
EI-MS: 379 (100, Mþ), 321 (18), 294 (54), 266 (76), 237 (98). HR-MS: 379.1521 (C21H21N3Oþ4 ; calc.
379.1532).
7-Chloro-1-(2,6-dimethylphenyl)-3-phenylquinoxalin-2(1H)-one (3a): Beige crystals. M.p. 175 – 1788
(hexane). 1H-NMR (600 MHz, CDCl3): 2.02 (s, 6 H); 6.52 (d, J ¼ 2.2, 1 H); 7.29 – 7.31 (m, 2 H); 7.32 (dd,
J ¼ 8.6, 2.2, 1 H); 7.36 – 7.39 (m, 1 H); 7.47 – 7.51 (m, 3 H); 7.93 (d, J ¼ 8.6, 1 H); 8.42 – 8.45 (m, 2 H).
13C-NMR (150 MHz, CDCl3): 17.7; 113.8; 124.6; 128.1; 129.4; 129.6; 129.7; 130.8; 131.3; 131.8; 133.6;
133.6; 135.3; 135.5; 136.4; 153.2; 154.5. EI-MS: 360 (100, Mþ), 331 (14), 317 (29), 255 (25). HR-MS:
360.1021 (C22H1735ClN2Oþ; calc. 360.1029).
7-Chloro-1-(4-ethoxyphenyl)-5-methoxy-3-phenylquinoxalin-2(1H)-one (3b): Yellow crystals. M.p.
251 – 2538 (hexane/AcOEt). 1H-NMR (400 MHz, CDCl3): 1.48 (t, J ¼ 7.0, 3 H); 4.05 (s, 3 H); 4.14 (q, J ¼
7.0, 2 H); 6.31 (d, J ¼ 2.0, 1 H); 6.78 (d, J ¼ 2.0, 1 H); 7.08 – 7.14 (m, 2 H); 7.18 – 7.23 (m, 2 H); 7.42 – 7.46
(m, 3 H); 8.35 – 8.39 (m, 2 H). 13C-NMR (100 MHz, CDCl3): 14.8; 56.7; 63.9; 106.3; 107.7; 116.1; 122.4;
128.0; 128.1; 129.1; 129.7; 130.4; 135.8; 136.4; 136.5; 152.3; 154.8; 156.7; 159.6. EI-MS: 406 (100, Mþ), 377
(94), 349 (36). HR-MS: 406.1092 (C23H1935ClN2O3þ ; calc. 406.1084).
7-Methoxy-1-(4-methylphenyl)-3-phenylquinoxalin-2(1H)-one (3c): Yellow crystals. M.p. 217 – 2208
(AcOEt). 1H-NMR (500 MHz, (D6)DMSO): 2.45 (s, 3 H); 3.68 (s, 3 H); 5.96 (d, J ¼ 2.6, 1 H); 7.04 (dd,
J ¼ 8.9, 2.6, 1 H); 7.31 – 7.35 (m, 2 H); 7.45 – 7.49 (m, 5 H); 7.88 (d, J ¼ 8.9, 1 H); 8.21 – 8.25 (m, 2 H).
13C-NMR (125 MHz, (D6)DMSO): 20.8; 55.6; 99.0; 110.9; 127.3; 127.8; 128.1; 129.0; 129.8; 130.6; 131.1;
133.6; 135.9; 136.0; 138.7; 150.4; 154.0; 160.6. EI-MS: 342 (100, Mþ), 314 (28), 299 (57). HR-MS:
342.1364 (C22H18N2Oþ2 ; calc. 342.1368).
7-Methoxy-1-(4-methylphenyl)-3-(2-thienyl)quinoxalin-2(1H)-one (3d): Pale yellow solid. M.p.
231 – 2348. 1H-NMR (500 MHz, (D6)DMSO): 2.45 (s, 3 H); 3.67 (s, 3 H); 5.97 (d, J ¼ 2.6, 1 H); 7.04
(dd, J ¼ 8.9, 2.6, 1 H); 7.22 (dd, J ¼ 5.1, 3.8, 1 H); 7.32 – 7.35 (m, 2 H); 7.46 – 7.48 (m, 2 H); 7.79 (dd, J ¼ 5.1,
1.1, 1 H); 7.83 (d, J ¼ 8.9, 1 H); 8.29 (dd, J ¼ 3.8, 1.1, 1 H). 13C-NMR (125 MHz, (D6)DMSO)4): 44.5;
79.3; 122.8; 134.9; 150.8; 151.5; 151.8; 154.1; 154.2; 154.9; 157.0; 158.9; 162.5; 162.9; 169.0; 176.7; 183.9.
EI-MS: 348 (100, Mþ), 305 (58). HR-MS: 348.0918 (C20H16N2O2Sþ; calc. 348.0932).
7-Methoxy-1-(4-methylphenyl)-3-(pyridin-4-yl)quinoxalin-2(1H)-one (3e): Yellow crystals. M.p.
220 – 2238 (hexane/AcOEt). 1H-NMR (500 MHz, (D6)DMSO): 2.43 (s, 3 H); 3.67 (s, 3 H); 5.96 (d,
J ¼ 2.6, 1 H); 7.05 (dd, J ¼ 2.6, 8.8, 1 H); 7.30 – 7.33 (m, 2 H); 7.42 – 7.46 (m, 2 H); 7.91 (d, J ¼ 8.8, 1 H);
8.14 – 8.18 (m, 2 H); 8.67 – 8.91 (m, 2 H). 13C-NMR (125 MHz, (D6)DMSO): 21.3; 56.2; 99.4; 111.9;
123.3; 127.7; 128.6; 131.1; 132.1; 133.8; 136.9; 139.4; 143.3; 148.4; 150.1; 154.4; 161.9. EI-MS: 343 (100,
Mþ), 315 (21), 300 (37). HR-MS: 343.1335 (C21H17N3Oþ2 ; calc. 343.1321).
7-Chloro-1-(2,6-dimethylphenyl)-3-(6-methoxy-3-nitropyridin-2-yl)quinoxalin-2(1H)-one (3f):
White crystals. M.p. 247 – 2498 (AcOEt). 1H-NMR (500 MHz, (D6)DMSO): 1.96 (s, 6 H); 4.04 (s,
3 H); 6.47 (d, J ¼ 2.2, 1 H); 7.24 (d, J ¼ 9.0, 1 H); 7.36 – 7.39 (m, 2 H); 7.42 – 7.46 (m, 1 H); 7.58 (dd, J ¼ 8.6,
2.2, 1 H); 8.09 (d, J ¼ 8.6, 1 H); 8.59 (d, J ¼ 9.0, 1 H). 13C-NMR (125 MHz, (D6)DMSO): 16.9; 55.2;
112.6; 113.5; 125.1; 129.3; 130.0; 131.0; 132.0; 132.4; 133.6; 135.1; 136.2; 136.7; 140.0; 147.5; 151.9; 155.5;
166.0. EI-MS: 436 (7, Mþ), 419 (8), 390 (100). HR-MS: 436.0933 (C22H1735ClN4Oþ4 ; calc. 436.0938).

Helvetica Chimica Acta – Vol. 96 (2013)
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7-Methoxy-3-(6-methoxy-3-nitropyridin-2-yl)-1-(4-methylphenyl)quinoxalin-2(1H)-one (3g): Pale
1
yellow crystals. M.p. 214 – 2168 (hexane/AcOBu). H-NMR (500 MHz, CDCl3): 2.45 (s, 3 H); 3.74 (s,
3 H); 4.09 (s, 3 H); 6.23 (d, J ¼ 2.6, 1 H); 6.90 (d, J ¼ 9.0, 1 H); 6.94 (dd, J ¼ 8.9, 2.6, 1 H); 7.20 – 7.23 (m,
2 H); 7.37 – 7.40 (m, 2 H); 7.89 (d, J ¼ 8.9, 1 H); 8.39 (d, J ¼ 9.0, 1 H). 13C-NMR (125 MHz, CDCl3)4):
21.3; 55.0; 55.7; 99.7; 111.4; 111.9; 127.8; 130.9; 131.6; 132.7; 135.3; 136.5; 139.6; 140.1; 149.1; 152.3; 154.1;
161.7; 166.3. EI-MS: 418 (10, Mþ), 386 (8), 372 (100). HR-MS: 418.1266 (C22H18N4Oþ5 ; calc. 418.1277).
7-Methoxy-1-(4-methylphenyl)-3-(1-nitronaphthalen-2-yl)quinoxalin-2(1H)-one (3h). Yellow crys-
tals. M.p. 173 – 1768 (hexane/AcOEt). 1H-NMR (500 MHz, CDCl3): 2.46 (s, 3 H); 3.73 (s, 3 H); 6.19 (d,
J ¼ 2.6, 1 H); 6.93 (dd, J ¼ 8.9, 2.6, 1 H); 7.20 – 7.24 (m, 2 H); 7.39 – 7.42 (m, 2 H); 7.61 – 7.69 (m, 2 H); 7.85
(d, J ¼ 8.9, 1 H); 7.93 – 7.96 (m, 1 H); 8.00 (d, J ¼ 8.6, 1 H); 8.08 (d, J ¼ 8.6, 1 H); 8.10 – 8.13 (m, 1 H).
13C-NMR (125 MHz, CDCl3)4): 21.3; 55.7; 99.5; 111.7; 122.9; 124.7; 126.9; 127.8; 127.9; 128.1; 128.9; 131.0;
131.2; 131.8; 132.9; 134.3; 136.4; 139.6; 147.4; 150.4; 154.1; 161.8. EI-MS: 437 (2, Mþ), 405 (2), 391 (100).
HR-MS: 437.1386 (C26H19N3Oþ4 ; calc. 437.1376).
7-Chloro-3-(5-chloro-2-nitrophenyl)-1-(4-ethoxyphenyl)-5-methoxyquinoxalin-2(1H)-one (3i): Yel-
low crystals. M.p. 219 – 2238 (hexane/AcOEt). 1H-NMR (500 MHz, CDCl3): 1.46 (t, J ¼ 7.1, 3 H); 4.06 (s,
3 H); 4.10 (t, J ¼ 7.1, 2 H); 6.38 (d, J ¼ 1.9, 1 H); 6.83 (d, J ¼ 1.9, 1 H); 7.05 – 7.09 (m, 2 H); 7.14 – 7.18 (m,
2 H); 7.55 (dd, J ¼ 8.7, 2.4, 1 H); 7.78 (d, J ¼ 2.4, 1 H); 8.07 (d, J ¼ 8.7, 1 H). 13C-NMR (125 MHz, CDCl3 ):
14.8; 56.8; 63.9; 106.7; 108.1; 116.1; 122.2; 125.5; 127.3; 129.1; 130.3; 132.0; 133.2; 136.9; 137.7; 140.3;
147.2; 153.1; 154.0; 156.9; 159.8. EI-MS: 485 (22, Mþ), 439 (100). HR-MS: 485.0537 (C23H1735Cl2N3O5þ ;
calc. 485.0545).
3-(5-Chloro-2-nitrophenyl)-7-methoxy-1-(4-methylphenyl)quinoxalin-2(1H)-one (3j): Yellowish
crystals. M.p. 181 – 1838 (hexane/AcOEt). 1H-NMR (500 MHz, CDCl3): 2.45 (s, 3 H); 3.74 (s, 3 H);
6.20 (d, J ¼ 2.5, 1 H); 6.95 (dd, J ¼ 8.8, 2.5, 1 H); 7.14 – 7.19 (m, 2 H); 7.37 – 7.40 (m, 2 H); 7.54 (dd, J ¼ 8.6,
2.3, 1 H); 7.79 (d, J ¼ 2.3, 1 H); 7.87 (d, J ¼ 8.8, 1 H); 8.05 (d, J ¼ 8.6, 1 H). 13C-NMR (125 MHz, CDCl3 ):
21.3; 55.7; 99.7; 111.6; 125.5; 127.7; 127.8; 130.0; 131.0; 131.6; 131.8; 132.7; 133.2; 136.4; 139.7; 139.9; 147.4;
151.4; 154.1; 161.8. EI-MS: 421 (19, Mþ), 375 (100). HR-MS: 421.0812 (C22H1635ClN3Oþ4 ; calc. 421.0829).
7-Chloro-1-(2,6-dimethylphenyl)quinoxalin-2(1H)-one (4a): Gray crystals. M.p. 103 – 1058 (hexane).
1H-NMR (500 MHz, CDCl3): 1.99 (s, 6 H); 6.53 (d, J ¼ 2.1, 1 H); 7.27 – 7. 33 (m, 3 H); 7.36 – 7.40 (m, 1 H);
7.88 (d, J ¼ 8.5, 1 H); 8.41 (s, 1 H). 13C-NMR (125 MHz, CDCl3): 17.6; 114.2; 124.6; 129.4; 130.0; 131.4;
131.9; 132.7; 133.6; 135.4; 137.4; 151.2; 153.5. EI-MS: 284 (100, Mþ), 267 (25), 281 (16), 255 (93). HR-
MS: 284.0712 (C16H1335ClN2Oþ; calc. 284.0716).
5,7-Dichloro-1-(4-ethoxyphenyl)quinoxalin-2(1H)-one (4b): Yellow crystals. M.p. 218 – 2208 (hex-
1
ane/AcOBu). H-NMR (500 MHz, CDCl3): 1.48 (t, J ¼ 6.8, 3 H); 4.12 (q, J ¼ 6.8, 2 H); 6.67 (d, J ¼ 2.0,
1 H); 7.10 – 7.13 (m, 2 H); 7.14 – 7.17 (m, 2 H); 7.42 (d, J ¼ 2.0, 1 H); 8.44 (s, 1 H). 13C-NMR (125 MHz,
CDCl3)4): 14.7; 63.9; 114.6; 116.3; 124.9; 126.6; 128.6; 129.0; 135.8; 136.6; 151.0; 154.5; 160.0. EI-MS: 334
(100, Mþ), 278 (94). HR-MS: 334.0270 (C16H1235Cl2N2Oþ2 ; calc. 334.0276).
7-Chloro-1-(4-chlorophenyl)quinoxalin-2(1H)-one (4c): White solid. M.p. 175 – 1808. 1H-NMR
(500 MHz, CDCl3): 6.69 (d, J ¼ 2.1, 1 H); 7.22 – 7.25 (m, 2 H); 7.31 (d, J ¼ 8.6, 2.1, 1 H); 7.61 – 7.65 (m,
2 H); 7.84 (d, J ¼ 8.6, 1 H); 8.35 (s, 1 H). 13C-NMR (125 MHz, CDCl3): 115.1; 124.6; 129.5; 130.9; 131.4;
131.7; 133.0; 134.6; 136.1; 137.1; 150.6; 154.2. EI-MS: 290 9 (100, Mþ), 262 (96). HR-MS: 290.0001
(C14H835Cl2N2Oþ; calc. 290.0014).
7-Chloro-1-(4-ethoxyphenyl)-5-methoxyquinoxalin-2(1H)-one (4d): White crystals. M.p. > 2508
1
(AcOEt). H-NMR (600 MHz, CDCl3): 1.48 (t, J ¼ 7.0, 3 H); 4.05 (s, 3 H); 4.11 (q, J ¼ 7.0, 2 H); 6.34
(d, J ¼ 2.1, 1 H); 6.78 (d, J ¼ 2.1, 1 H); 7.08 – 7.11 (m, 2 H); 7.14 – 7.17 (m, 2 H); 8.33 (s, 1 H). 13C-NMR
(150 MHz, CDCl3): 14.8; 56.7; 63.9; 106.4; 108.0; 116.1; 122.5; 127.1; 129.0; 136.4; 137.6; 148.6; 155.1;
156.7; 159.8. EI-MS: 330 (100, Mþ), 301 (83), 273 (45), 245 (17). HR-MS: 330.0785 (C17H1535ClN2Oþ3 ;
calc. 330.0771).
7-Chloro-1-(4-ethoxyphenyl)-3-ethyl-5-methoxyquinoxalin-2(1H)-one (4e): White solid. M.p. 213 –
1
2178 (hexane/AcOEt). H-NMR (500 MHz, CDCl3): 1.36 (t, J ¼ 7.5, 3 H); 1.47 (t, J ¼ 7.5, 3 H); 3.01 (q,
J ¼ 7.5, 2 H); 4.04 (s, 3 H); 4.12 (q, J ¼ 7.5, 2 H); 6.29 (d, J ¼ 2.0, 1 H); 6.75 (d, J ¼ 2.0, 1 H); 7.06 – 7.10 (m,
2 H); 7.13 – 7.17 (m, 2 H). 13C-NMR (125 MHz, CDCl3 ): 11.3; 14.8; 28.0; 56.8; 63.9; 106.3; 107.9; 116.0;
121.8; 127.9; 129.1; 135.6; 136.3; 154.8; 156.2; 159.6; 161.2. EI-MS: 358 (100, Mþ), 329 (96), 301 (36). HR-
MS: 358.1076 (C19H1935ClN2Oþ3 ; calc. 358.1084).

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7-Chloro-1-(2,6-dimethylphenyl)-3-ethylquinoxalin-2(1H)-one (4f): Gray solid. M.p. 79 – 828.
1H-NMR (500 MHz, CDCl3): 1.37 (t, J ¼ 7.5, 3 H); 1.96 (s, 6 H); 3.02 (q, J ¼ 7.5, 2 H); 6.47 (d, J ¼ 2.1,
1 H); 7.25 – 7.29 (m, 3 H); 7.33 – 7.37 (m, 1 H); 7.83 (d, J ¼ 8.5, 1 H). 13C-NMR (125 MHz, CDCl3): 10.5;
17.6; 27.3; 113.9; 124.3; 129.3; 129.6; 130.5; 131.3; 133.4; 134.5; 135.3; 135.5; 153.3; 163.2. EI-MS: 312 (100,
Mþ), 283 (37), 255 (88). HR-MS: 312.1035 (C18H1735ClN2Oþ; calc. 312.1029).
3-Ethyl-7-methoxy-1-(4-methylphenyl)quinoxalin-2(1H)-one (4g): White crystals. M.p. 152 – 1558
(hexane/AcOEt). 1H-NMR (500 MHz, CDCl3): 1.35 (t, J ¼ 7.4, 3 H); 2.46 (s, 3 H); 2.95 (q, J ¼ 7.4, 2 H);
3.70 (s, 3 H); 6.12 (d, J ¼ 2.6, 1 H); 6.86 (dd, J ¼ 8.9, 2.6, 1 H); 7.13 – 7.16 (m, 2 H); 7.37 – 7.40 (m, 2 H);
7.76 (d, J ¼ 8.9, 1 H). 13C-NMR (125 MHz, CDCl3): 10.9; 21.3; 27.1; 55.5; 99.7; 110.6; 127.6; 127.8; 130.4;
130.9; 133.3; 135.5; 139.3; 155.0; 159.3; 160.1. EI-MS: 294 (100, Mþ), 265 (15), 251 (37). HR-MS:
294.1362 (C18H18N2Oþ2 ; calc. 294.1368).
1-(2,6-Dimethylphenyl)-3-ethyl-7-phenylquinoxalin-2(1H)-one (4h): Beige crystals. M.p. 1578 (hex-
ane/AcOEt). 1H-NMR (500 MHz, CDCl3): 1.40 (t, J ¼ 7.4, 3 H); 1.99 (s, 6 H); 3.05 (q, J ¼ 7.4, 2 H); 6.67
(d, J ¼ 2.0, 1 H); 7.25 – 7.28 (m, 2 H); 7.31 – 7.35 (m, 2 H); 7.37 – 7.43 (m, 4 H); 7.55 (dd, J ¼ 8.2, 2.0, 1 H);
7.96 (d, J ¼ 8.2, 1 H). 13C-NMR (125 MHz, CDCl3): 10.7; 17.7; 27.4; 112.3; 123.0; 127.3; 128.0; 128.9; 129.2;
129.4; 129.7; 132.2; 132.8; 133.8; 135.4; 139.9; 142.7; 153.7; 162.9. EI-MS: 354 (100, Mþ), 325 (20), 297
(71). HR-MS: 354.1728 (C24H22N2Oþ; calc. 354.1732).
1-(2,6-Dimethylphenyl)-7-phenylquinoxalin-2(1H)-one (4i): Gray crystals. M.p. 144 – 1478 (hexane/
AcOEt). 1H-NMR (500 MHz, CDCl3): 2.02 (s, 6 H); 6.72 (d, J ¼ 1.9, 1 H); 7.27 – 7.30 (m, 2 H); 7.34 – 7.39
(m, 2 H); 7.40 – 7.43 (m, 4 H); 7.58 (dd, J ¼ 8.3, 1.9, 1 H); 8.01 (d, J ¼ 8.3, 1 H); 8.45 (s, 1 H). 13C-NMR
(125 MHz, CDCl3)4): 17.6; 112.5; 132.3; 127.3; 128.3; 129.0; 129.3; 129.7; 130.6; 133.0; 133.1; 135.5; 139.5;
144.4; 150.9; 154.0. EI-MS: 326 (100, Mþ), 297 (98). HR-MS: 326.1414 (C22H18N2Oþ; calc. 326.1419).
7-Chloro-1-(4-ethoxyphenyl)-5-methoxy-3-methylquinoxalin-2(1H)-one (4j): White solid. M.p. 249 –
2548. 1H-NMR (500 MHz, CDCl3): 1.47 (t, J ¼ 7.0, 3 H); 2.64 (s, 3 H); 4.04 (s, 3 H); 4.11 (q, J ¼ 7.0, 2 H);
6.29 (d, J ¼ 2.0, 1 H); 6.76 (d, J ¼ 2.0, 1 H); 7.07 – 7.11 (m, 2 H); 7.13 – 7.16 (m, 2 H). 13C-NMR (125 MHz,
CDCl3): 14.7; 21.6; 56.7; 63.8; 106.1; 107.9; 116.0; 121.6; 127.8; 129.0; 135.6; 136.3; 155.2; 155.9; 157.4;
159.6. EI-MS: 344 (100, Mþ), 329 (16), 315 (97) 287 (48). HR-MS: 344.0939 (C18H1735ClN2Oþ3 ; calc.
344.0928).
7-Methoxy-1-(4-methylphenyl)quinoxalin-2(1H)-one (4k): Gray crystals. M.p. 133 – 1358 (hexane/
AcOEt). 1H-NMR (500 MHz, CDCl3): 2.47 (s, 3 H); 3.71 (s, 3 H); 6.16 (d, J ¼ 2.6, 1 H); 6.90 (dd, J ¼ 9.1,
2.6, 1 H); 7.15 – 7.18 (m, 2 H); 7.39 – 7.43 (m, 2 H); 7.81 (d, J ¼ 9.1, 1 H); 8.23 (s, 1 H). 13C-NMR
(125 MHz, CDCl3): 21.3; 55.6; 99.7; 111.1; 127.7; 128.3; 134.1; 131.4; 132.6; 135.8; 139.7; 147.5; 155.3;
161.4. EI-MS: 266 (100, Mþ), 238 (22), 223 (60). HR-MS: 266.1048 (C16H14N2Oþ2 ; calc. 266.1055).
7-Methoxy-3-methyl-1-(4-methylphenyl)quinoxalin-2(1H)-one (4l): White solid. M.p. 155 – 1608.
1H-NMR (400 MHz, CDCl3): 2.47 (s, 3 H); 2.59 (s, 3 H); 3.70 (s, 3 H); 6.12 (d, J ¼ 2.6, 1 H); 6.87 (dd, J ¼
8.9, 2.6, 1 H); 7.12 – 7.17 (m, 2 H); 7.38 – 7.42 (m, 2 H); 7.75 (d, J ¼ 8.9, 1 H). 13C-NMR (100 MHz, CDCl3):
21.1; 21.3; 55.5; 99.7; 110.7; 127.4; 127.8; 130.1; 130.9; 133.2; 135.7; 139.4; 155.3; 155.6; 160.2. EI-MS: 280
(100, Mþ), 252 (48), 237 (82). HR-MS: 280.1216 (C17H16N2Oþ2 ; calc. 280.1212).
7-Chloro-1-(pyridin-4-yl)quinoxalin-2(1H)-one (4m): Yellow solid. M.p. 204 – 2098. 1H-NMR
(500 MHz, (D6)DMSO): 6.60 (d, J ¼ 2.1, 1 H); 7.46 (dd, J ¼ 8.6, 2.1, 1 H); 7.56 – 7.58 (m, 2 H); 7.93 (d,
J ¼ 8.6„ 1 H); 8.36 (s, 1 H); 8.89 – 8.92 (m, 2 H). 13C-NMR (125 MHz, (D6)DMSO): 114.8; 124.2; 124.5;
131.7; 131.8; 134.5; 135.7; 143.2; 151.7; 152.6; 153.7. EI-MS: 257 (100, Mþ), 229 (64). HR-MS: 257.0351
(C13H835ClN3Oþ; calc. 257.0356).
7-Chloro-1-phenylquinoxalin-2(1H)-one (4n): Beige powder. M.p. 189 – 1928 (hexane/AcOEt) ([17]:
187 – 1898). 1H-NMR (500 MHz, CDCl3): 6.69 (d, J ¼ 2.1, 1 H); 7.27 – 7.31 (m, 3 H); 7.57 – 7.61 (m, 1 H);
7.64 – 7.67 (m, 2 H); 7.84 (d, J ¼ 8.7, 1 H); 8.37 (s, 1 H). 13C-NMR (125 MHz, CDCl3): 115.4; 124.4; 128.1;
130.0; 130.6; 131.2; 131.7; 134.7; 134.9; 136.9; 150.8; 154.4. EI-MS: 256 9 (100, Mþ), 228 (87). HR-MS:
256.0394 (C14H935ClN2Oþ; calc. 256.0403).
N3-(2,6-Dimethylphenyl)[1,1’-biphenyl]-3,4-diamine (5): Gray crystals. M.p. 247 – 2498 (hexane/
AcOEt). 1H-NMR (500 MHz, CDCl3): 2.20 (s, 6 H); 3.7 (br. s, 2 H); 4.89 (br. s, 1 H); 6.49 (s, 1 H); 6.85
(d, J ¼ 7.9, 1 H); 7.00 – 7.04 (m, 2 H); 7.09 – 7.12 (m, 2 H); 7.18 – 7.22 (m, 1 H); 7.28 – 7.32 (m, 2 H); 7.35 –
7.38 (m, 2 H). 13C-NMR (125 MHz, CDCl3): 18.3; 114.1; 116.4; 119.5; 124.4; 126.2; 126.6; 128.5; 128.7;

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132.9; 133.2; 134.4; 135.5; 139.5; 141.5. EI-MS: 288 (100, Mþ). HR-MS: 288.1631 (C20H20N2þ ; calc.
288.1626).
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Received June 14, 2012