Tert -Butyl Hypochlorite Induced Cyclization of Ethyl 2-(N -Aryl-carbamoyl)-2-iminoacetates

Article abstract of DOI:10.1055/s-0036-1588462

Ethyl 2-(N -arylcarbamoyl)-2-iminoacetates can be transformed into the corresponding quinoxalin-2-ones in high yield by using the oxidation system of tert -butyl hypochlorite, tetrabutylammonium iodide and tetrabutylammonium chloride. Oxygen exhibits a be

Full text of DOI:10.1055/s-0036-1588462

SYNTHESIS
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©
Georg Thieme Verlag Stuttgart · New York
2017, 49, A–I
special topic
A
en
Synthesis
D. Li et al.
Special Topic
tert-Butyl Hypochlorite Induced Cyclization of Ethyl 2-(N-Aryl-
carbamoyl)-2-iminoacetates
t-BuOCl (2.0 equiv)
Dianjun Li
(
n-Bu)4N
I
(1.5 equiv)
O
N
CO2Et
O
Ying Li*
Wei Yu*
R1
(
n-Bu)4N Cl (3.0 equiv)
DCE, O2, 80 °C
CO2Et
R1
N
N
R2
R2
NH
State Key Laboratory of Applied Organic Chemistry,
College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, P. R. of China
liying@lzu.edu.cn
24 examples, up to 94%
Iminyl radical
cyclization
Deoxygenative
1,2-migration
–
O2
yuwei@lzu.edu.cn
OO
N
O2
N
Published as part of the Special Topic Modern
Cyclization Strategies in Synthesis
CO2Et
2
CO Et
R1
R1
N
R2
N
R2
O
O
Homolytic aromatic substitution promoted by oxygen
Received: 12.04.2017
H
Accepted after revision: 22.05.2017
Published online: 03.07.2017
DOI: 10.1055/s-0036-1588462; Art ID: ss-2017-c0243-st
HAS
– H
or [O], – H+
Abstract Ethyl 2-(N-arylcarbamoyl)-2-iminoacetates can be trans-
formed into the corresponding quinoxalin-2-ones in high yield by using
the oxidation system of tert-butyl hypochlorite, tetrabutylammonium
iodide and tetrabutylammonium chloride. Oxygen exhibits a beneficial
effect on the reaction. The reaction is proposed to follow an iminyl rad-
ical cyclization mechanism where azaspirocyclohexadienylperoxyl radi-
cal is formed as a key intermediate. The quinoxalin-2-one is derived
from the azaspirocyclohexadienylperoxyl radical via concurrent oxygen
extrusion and rearrangement.
spirocyclic products or
others
Scheme 1 Illustration of intramolecular HAS
8
and our group have investigated the applicability of the cy-
clization of α-(aminocarbonyl)iminyl radicals for the syn-
thesis of quinoxalin-2-ones. In one of our investigations, we
used the reagent combination of tert-butyl hydroperoxide
Key words cyclization, radical reaction, iminyl radical, quinoxalin-2-
ones, oxygen, peroxyl radical
(TBHP) and tetrabutylammonium iodide (TBAI) to effect the
Homolytic aromatic substitution (HAS) reactions have
long been explored for their potential usefulness in the syn-
thesis of aromatic compounds. In this context, numerous
generation of α-(aminocarbonyl)iminyl radicals from ethyl
2-(N-arylcarbamoyl)-2-iminoacetates.8a Under the indicat-
ed oxidative conditions, the composition of the products
varied according to whether oxygen was present in the re-
action system. When the reactions were conducted under
an oxygen atmosphere, azaspirocyclohexadienones were
1
studies have been devoted to applying intramolecular HAS
reactions to the synthesis of polycyclic aromatic com-
pounds. In intramolecular HAS, the radical center can at-
tack the aromatic ring at the ipso-position as well as the
ortho-position relative to the tether, with the former path-
way often being more favored (Scheme 1). Although the
thus-formed spirocyclohexadienyl radicals are liable to un-
dergo 1,2-migration to give the corresponding fused cyclo-
9
predominantly generated in most cases. When the reac-
tions were conducted under an argon atmosphere, on the
other hand, quinoxalin-2-one products were obtained in a
significant amount; in some cases, they became the major
product. These results support the mechanism where cy-
clization of iminyl radical A to azaspirocyclohexadienyl rad-
ical B is a fast process, and azaspirocyclohexadienone is de-
rived from trapping of B by oxygen (Scheme 2). To further
elucidate the influence of oxygen and related mechanistic
issues, we continued our research by using tert-butyl hypo-
chlorite (t-BuOCl) as oxidant to replace TBHP. We found that
when t-BuOCl was used in combination with TBAI, quinox-
alin-2-ones were generated as the major product. The reac-
tion was improved noticeably by exposure to oxygen and
tetrabutylammonium chloride (TBAC). It is noteworthy that
2
hexadienyl radicals, this pathway often fails to occur due
to fast competitive pathways, especially when the cycliza-
3,4
tion involves 5-exo-ipso attack. Therefore, to enlarge the
scope of intramolecular HAS in synthetic applications, vari-
ous factors affecting the cyclizations and subsequent trans-
formations need to be fully comprehended.
The cyclization of iminyl radicals constitutes an import-
5
ant strategy for the synthesis of nitrogen heterocycles. Re-
6
7
cently, Spagnolo and co-workers, Zhang and co-workers
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

B
Synthesis
D. Li et al.
Special Topic
under the t-BuOCl-based conditions, no azaspirocyclic
products were obtained, except in one case. This result is
consistent with an intramolecular HAS mechanism that in-
volves the formation and subsequent 1,2-migration of
azaspirocyclohexadienylperoxyl radical. A comparison of
the current results with those obtained under the TBHP-
based conditions reveals some interesting points about the
involvement of oxygen in HAS reactions. Herein, we report
this study in detail.
greatly reduced the yield of 2a (Table 1, entry 13), and no
reaction took place in the absence of t-BuOCl (Table 1, entry
14).
Table 1 Screening of Conditions for the Reaction of 1aa
N
CO2Et
O
t-BuOCl
TBAI, TBAC
O
CO2Et
+
CO2Et
N
N
O
N
Bn
NH
Bn
Bn
O
1a
2a
3a
OO
O
Entry
Additive
TBAI
Solvent
Atmosphere Yield (%)b
N
N
CO2Et
CO2Et
R1
TBAC
(equiv)
2a
3a
R1
N
R2
C
N
(
equiv)
R2
O
O
1
2
1.5
3.0
1.5
1.5
1.5
1.5
1.5
0
0
DCE
air
45
30
0
DCE
air
64
15
fast O2
HN
CO2Et TBHP/
TBAI
CO2Et
O
3
2.0
2.0
3.0
3.0
3.0
1.5
3.0
3.0
1.0
3.0
3.0
3.0
3.0
3.0
3.0
DCE
air
80
5
N
R1
fast
R1
N
4
DCE
O2
82
5
3
CO2Et
N
O
N
R1
N
R2
R2
R2
5
DCE
air
85
O
A
B
6
DCE
argon
61
8
7
DCE
O
2
91
trace
8
DCE
O
2
mixture
52
H
N
N
CO2Et
O
2
CO Et
9c
10d
O], – H+
1.5
1.5
1.5
0.5
1.5
1.5
1.5
1.5
1.5
DCE
O2
3
16
27
23
22
[
R1
R1
N
R2
N
R2
O
DCE
O
O
O
O
O
O
O
O
2
2
2
2
2
2
2
2
32
1
1
1
1
1
1
DCE
55
D
2
DCE
59
Scheme 2 Proposed mechanism for the TBHP-promoted oxidative cy-
clization of ethyl 2-(N-arylcarbamoyl)-2-iminoacetates
3e
4f
5
DCE
45
8a
DCE
N.R.g
63
THF
9
We began our study by screening the reaction condi-
tions on the basis of our previous investigation, with ethyl
-(benzyl(phenyl)amino)-2-imino-3-oxopropanoate (1a) as
8a
16
toluene
1,4-dioxane
82
trace
4
17
80
3
a
b
c
d
e
f
the model compound. It has been long known that imines
t-BuOCl (2.0 equiv) was used, at 80 °C, unless otherwise specified.
Isolated yield.
Reaction temperature was 100 °C.
Reaction temperature was 50 °C.
t-BuOCl (1.0 equiv) was used.
In the absence of t-BuOCl.
No reaction took place.
can be chlorinated to N-chloroimines with t-BuOCl.8
b,10
As
such, when 1a was subjected to t-BuOCl (2.0 equiv) in 1,2-
dichloroethane (DCE) at 80 °C, ethyl 3-(benzyl(phenyl)ami-
no)-2-(chloroimino)-3-oxopropanoate was obtained in 80%
yield. When the reaction was performed in the presence of
TBAI, on the other hand, quinoxalin-2-one product 2a was
obtained, along with a significant amount of compound 3a
g
The optimal reaction conditions (Table 1, entry 7) were
then applied to a variety of ethyl 2-(N-arylcarbamoyl)-2-
iminoacetates 1; the results are summarized in Scheme 3. It
can be seen that the expected cyclization occurred un-
eventfully for the tested substrates, affording the corre-
sponding quinoxalin-2-one products 2, mostly in good
yields. The yields are, in general, comparable with those
achieved under visible-light irradiation conditions with
ethyl 2-(N-arylcarbamoyl)-2-(chloroimino)acetates as pre-
cursors.8b This protocol is of practical value as it can be ap-
plied on a gram scale. Noticeably, no azaspirocyclic product
was obtained in all these reactions, except for compound
1g, in which case azaspirocyclohexadienone 4g was ob-
tained as the major product. For substrates bearing a sub-
stituent at the meta-position of the N-phenyl ring, two re-
(Table 1, entries 1 and 2). The yield of 2a could be raised by
the addition of TBAC (Table 1, entries 3–7). Oxygen proved
to be beneficial to the cyclization process: the yield of 2a
could be increased to 91% when the reaction was per-
formed under an oxygen atmosphere (Table 1, entry 7),
whereas under argon atmosphere, it dropped to 61% (Table
1, entry 6). Further testing of the reaction conditions indi-
cated that a suitable reaction temperature is 80 °C (Table 1,
entries 9 and 10), while solvents like toluene, THF and 1,4-
dioxane are inferior to DCE for the current transformation
(Table 1, entries 15–17). Lowering the amount of t-BuOCl
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

C
Synthesis
D. Li et al.
Special Topic
gioisomers were obtained (2k–2p), with the sterically more
hindered one being the major product regardless of the
electronic nature of the substituent.
ated under oxygen atmosphere for the same substrates;
when the reaction was performed under an argon atmo-
sphere, both azaspirocyclic products and quinoxalin-2-ones
were obtained, the ratio of which was dependent on the
t-BuOCl (2.0 equiv)
TBAI (1.5 equiv)
TBAC (3.0 equiv)
8a
property and position of substituents. As illustrated in
N
CO2Et
O
O
R1
R1
Scheme 2, it has been proved that in the TBHP/TBAI-medi-
ated reactions, the azaspirocyclohexadienone and quinox-
alin-2-one are derived from a common azaspirocyclohexa-
dienyl radical intermediate B, trapping of which by oxygen
would yield the azaspirocyclohexadienone. One ready ex-
planation for this apparent discrepancy is that under the
current t-BuOCl-based conditions, the reaction might occur
through a non-radical pathway where the cyclization in-
volves electrophilic aromatic substitution of an N-iodo-
imine intermediate (Scheme 5). It is well known that t-BuOCl
can react with iodide to generate t-BuOI, which is a power-
CO2Et
N
DCE, O2, 80 °C
N
R2
NH
CO2Et
R2
R1
R1
N
N
CO2Et
O
N
CO2Et
N
O
+
N
R1
N
O
Bn
2a 91% (70%a)
R1 = H
Bn
Bn
R1 = Me 2b 86%
R1 = OMe 2c 80%
R1 = OMe 2k-1
2k-2 81% (67:33)
2l-2 66% (78:22)
R1 = Me
R1 = i-Pr
R1 = Br
R1 = Cl
2l-1
R1 = F
R1 = Cl
2d 74%
2e 56%
2m-1
2n-1
2o-1
2m-2 89% (60:40)
2n-2 77% (80:20)
2o-2 94% (73:27)
R1 = Br
R1 = I
2f 73%
2g 20%b
R1 = CF3
2p-1
2p-2 70% (57:43)
11
ful iodinating reagent. In a relevant study concerning the
R1 = CF3 2h 64%
R1 = Ph 2i 71%
N
CO2Et
N
N
CO2Et
reaction of unsaturated N-chloroamines with TBAI, Noack
and Göttlich proposed an electrophilic addition mechanism
Me
N
R2
O
O
12
N
CO2Et
to account for their results. Analogously, an electrophilic
R2 = Me 2q 61%
aromatic substitution mechanism might be advanced for
the present reactions. Despite its ostensible reasonableness,
however, this mechanism cannot explain why the reaction
can be considerably enhanced by the addition of TBAC,
which should suppress the formation of an N-iodoimine in-
termediate. Besides, it cannot explain the beneficial effect
2
t
68%
Me
N
O
R2 = Et 2r 67%
Bn
R2 = Ph 2s 83%
2
j
77%
O
N
CO2Et
N
CO2Et
N
O
N
Bn
Bn
O
2
u
40%
4g
Cl
N
CO2Et
O
Scheme 3 t-BuOCl-mediated reactions of compounds 1 under oxygen
t-BuOCl
R1
atmosphere. Reactions were conducted on a 0.5-mmol scale; isolated
N
a
b
yields are given. Reaction was conducted on a 5.0-mmol scale. Be-
R2
sides 2g, 4g was obtained in 64% yield.
1
Cl
I
I
To further demonstrate the influence of a substituent,
the standard reaction conditions were then applied to com-
pounds 1v–1x. As shown in Scheme 4, the substituent at
the phenyl ring exerts a moderate influence on the cycliza-
tion, with a tendency that an electron-donating group is
comparatively more beneficial.
H
N
CO2Et
O
N
CO2Et
O
– I
R1
R1
Cl
t-BuOI
N
N
R2
R2
H+
–
t-BuOCl
I
2
These results show some striking differences from those
under the TBHP-based reaction conditions. When TBHP
was used as oxidant, azaspirocyclohexadienones (or azaspi-
rocyclohexadienyl peroxides) were overwhelmingly gener-
Scheme 5 Alternative electrophilic aromatic substitution mechanism
for the t-BuOCl-promoted reaction of ethyl 2-(N-arylcarbamoyl)-2-imi-
noacetates
R1
R1
N
N
CO Et
R1
2
O
t-BuOCl (2.0 equiv)
TBAI (1.5 equiv)
TBAC (3.0 equiv)
O
CO2Et
CO2Et
N
O
N
+
NH
DCE, O2, 80 °C
N
v, R1 = OMe
w, R1 = Me
65%
82%
2v-1
(~3:2)
(~3:2)
2v-2
1
1
2w-1
2w-2
x, R1 = Br
51%
2x-1
(~2:3)
2x-2
1
Scheme 4 Reactions indicating a substituent effect
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

D
Synthesis
D. Li et al.
Special Topic
of oxygen on the reaction. Therefore, we speculate that the
present reactions still involve generation and cyclization of
an iminyl radical, as proposed in our previous study.8
In this radical mechanism (Scheme 6), the iminyl radical
A is formed via a single-electron transfer (SET) between the
initially formed N-chloroimine intermediate and iodide.
The subsequent cyclization of A would provide quinoxalin-
shown in Scheme 6, after the iminyl radical A is formed, it
would undergo ipso- or ortho-attacking cyclization to afford
radical B or D. The ipso-attacking cyclization (path (a)) is
faster than the ortho-attacking cyclization (path (b)); thus,
radical B should be formed preferentially. In the absence of
oxygen, radical B would revert to radical A, or rearrange to
radical D (path (d)); in the presence of oxygen, it would be
2
-one products 2. The beneficial effect of TBAC is attributed
rapidly trapped by oxygen to give peroxyl radical C (path
to its function of suppressing the conversion of N-chloro-
imine into N-iodoimine intermediate F, which can be
formed via nucleophilic substitution by the iodide (the
presence of chloride would reverse this substitution pro-
cess). Consequently, a sufficient amount of iodide anion is
available in the reaction system to participate in the SET
process of forming iminyl radical A. Moreover, intermediate
F might be responsible for the formation of 3 and other by-
products, and thus its suppression would help to improve
the yield of the main product.
The radical route shown in Scheme 6 is supported by
the observed regioselectivities for compounds 2k–2p,
which are close in value to those observed under photo-
chemical conditions. However, the product ratios for the
reactions of compounds 1v–1x are different from those un-
der photochemical conditions. This might be due to the
change of conditions such as solvent and reaction tempera-
ture. Nonetheless, these latter selectivities, as they are not
high, also point to a homolytic, rather than an electrophilic,
substitution mechanism.
(c)).1
3,14
It has long been established that a peroxyl radical
can readily abstract a hydrogen atom from TBHP to give the
corresponding peroxide and tert-butyl peroxyl radical (t-
BuOO·).15 Thus, under the conditions of TBHP, radical C
would react with TBHP to yield the corresponding peroxide.
The thus-formed peroxide then undergoes dehydration to
afford azaspirocyclohexadienone.1
4c
Besides this route,
there is another pathway towards azaspirocyclohexadien-
ones. Under the conditions of TBHP/TBAI, tert-butoxyl radi-
cal (t-BuO·) would be produced: it not only acts as an active
16
oxidant, but also can react with TBHP to generate t-BuOO·.
Radical B is labile to coupling with t-BuOO· to give azaspiro-
cyclic product E (path (e)). This coupling is expected to be
favorable due to the persistent radical effect of t-BuOO·
(peroxyl radicals can be viewed as a type of persistent radi-
8b
17 18
cal ). Peroxide E can be transformed into azaspirocyclo-
19,20
hexadienone via the Kornblum–DeLaMare reaction.
This latter process is responsible for the formation of
azaspirocyclic products in the absence of oxygen under
TBHP/TBAI conditions.8a
If the radical mechanism operates for the present reac-
tions, then questions arise: why are no azaspirocyclic prod-
ucts generated under the present conditions? Why does ox-
ygen even help to increase the yield of compounds 2 (Table
When t-BuOCl is used in place of TBHP, on the other
hand, there would be neither TBHP nor tert-butyl peroxyl
radical in the reaction system, although t-BuOCl can serve
as a source of t-BuO·.21 The cyclohexadienylperoxyl radical
C has no alternative pathway but to be transformed into
radical D via rearrangement and extrusion of oxygen (path
1)? We reason that the answer has to be found in the differ-
ence between the two oxidants, TBHP and t-BuOCl. As
I
3
+ others
HN
N
CO Et
N
2
CO2Et
t-BuOl
R1
R1
R1
R1
O
O
t-BuO
+
t-BuOOH
t-BuOH
+
t-BuOO
N
R2
1
R2
1
F
TBHP/
TBAI
t-BuOO
t-BuOCl
I
Cl
(g)
(b)
t-BuOO
N
(
ref. 8a)
CO2Et
E
Cl
N
fast
R1
I
N
R2
(
e)
2
CO Et
N
2
CO Et
O
I
/ –Cl
SET
(a)
N
R1
(a)
CO2Et
R1
N
R2
O
N
R2
O
N
R2
O
A
B
fast
(1) t-BuOOH
– t-BuOO
(
d)
O
(
b)
H
O2
fast
(
c)
N
N
CO2Et
(
2) – H2O
R1
OO
N
2
CO Et
N
2
CO Et
R2
O
[O], –H+
– O2
+ other products
R1
N
CO2Et
under the TBHP-based
conditions
N
O
N
O
slow
(f)
R1
N
R2
R2
R2
D
O
C
2
under the t-BuOCl-based conditions
Scheme 6 Plausible mechanism for the reaction of 1
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

E
Synthesis
D. Li et al.
Special Topic
(
f)). It has been established that hydrogen abstraction from
chemical shift of CDCl3 (δ = 77.00 ppm). Mass spectra (EI-MS) were
measured on an HP 5988A mass spectrometer by direct inlet at 70 eV.
High-resolution mass spectra (HRMS) were measured on a Bruker
micrOTOF QII instrument by ESI. Melting points were measured on an
XT-4 melting point apparatus and are uncorrected. Flash column
chromatography was carried out with silica gel (200–300 mesh). tert-
Butyl hypochlorite (t-BuOCl) was purchased from TCI Chemicals.
Tetrabutylammonium iodide (TBAI) and tetrabutylammonium chlo-
ride (TBAC) were purchased from Energy Chemicals and used without
organic substrates by a conjugated dienyl peroxyl radical is
a slow process, and consequently the conjugated diene per-
oxyl radical can undergo rearrangement.14 In the present
case, this rearrangement is accompanied by extrusion of
oxygen. As radical D would be readily rearomatized to com-
pound 2, the rearrangement from C to D should be an irre-
versible process. Among the three pathways ((b), (d) and (f))
guiding radical A to radical D, path (f) seems to be the most
favorable as oxygen can increase the yield of 2 remarkably,
though the other two occurrences cannot be ruled out.
When the reaction is conducted under an argon atmo-
sphere, the reverse process from radical B to radical A
would occur, and other pathways such as path (g) would
have a chance to compete, thus undermining the main reac-
tion.
2
further purification. 1,2-Dichloroethane (DCE) was distilled from P O5
under an argon atmosphere before use. Compounds 1 were prepared
8a
according to the previously reported method.
Cyclization of Ethyl 2-(N-Arylcarbamoyl)-2-iminoacetates 1; Gen-
eral Procedure
To a 35-mL tube equipped with a magnetic stirring bar were added an
ethyl 2-(N-arylcarbamoyl)-2-iminoacetate 1 (0.5 mmol, 1.0 equiv),
TBAI (277 mg, 0.75 mmol, 1.5 equiv), TBAC (425 mg, 1.5 mmol, 3.0
equiv), t-BuOCl (115 μL, 1.0 mmol, 2.0 equiv) and DCE (5 mL). The
tube was sealed with a rubber stopper, and then subjected to stirring
in an oil bath at 80 °C under an oxygen atmosphere (oxygen balloon).
After the reaction was complete (generally 1 to 1.5 h), as indicated by
TLC, the reaction mixture was poured into a saturated aqueous sodi-
um bisulfite solution (15 mL), and was extracted with EtOAc (10 × 3
mL). The combined organic layers were washed with brine (30 mL)
and dried with anhydrous sodium sulfate. The solvent was removed
under reduced pressure, and the residual was subjected to silica gel
chromatography (EtOAc–petroleum ether) to give product 2.
As shown in Scheme 3, when substrate bearing an io-
dine atom at the para-position of the N-phenyl ring was
used, the main product became the azaspirocyclic 4g. This
abnormality might be caused by the cleavage of C–I in C in
3
this case. The bond dissociation energy of C(sp )–I is weak
22
(56 kcal/mol for C H –I ), and the C–I dissociation leading
2 5
to 4g becomes competitive with the rearrangement to D.
In summary, we have demonstrated that ethyl 2-(N-
arylcarbamoyl)-2-iminoacetates can be transformed into
the corresponding quinoxalin-2-ones in high yield by using
the reagent combination of tert-butyl hypochlorite, tetra-
butylammonium iodide and tetrabutylammonium chloride.
The presence of oxygen is beneficial to the reaction, despite
not being incorporated into the final product. The results
revealed herein can be rationalized with a free-radical
mechanism that involves the cyclization of α-(aminocar-
bonyl)iminyl radicals. The beneficial effect of oxygen is at-
tributed to its fast trapping of the key azaspirocyclohexadi-
enyl radical intermediate. The thus-formed azaspirocyclo-
hexadienylperoxyl radical then undergoes concurrent
oxygen extrusion and rearrangement to give quinoxalin-2-
one products. A comparison of the present results with
those previously obtained under TBHP/TBAI conditions in-
dicates that the nature of the oxidant is critical in determin-
ing the reaction consequence. The use of TBHP would entail
the formation of oxygenated azaspirocyclic products,
whereas these products can be avoided by employing t-
BuOCl as the oxidant. Under the latter circumstance, the
radical rearrangement can become predominant due to the
lack of a fast, competitive hydrogen-abstraction pathway.
The current reactions not only provide a new protocol for
the preparation of quinoxalin-2-ones, they also reveal an
interesting oxygen involvement in HAS reactions.
Ethyl 4-Benzyl-3-oxo-3,4-dihydroquinoxaline-2-carboxylate
8
a,b
(2a)
Yellow solid; mp 93–94 °C; yield: 140 mg (91%).
1
H NMR (400 MHz, CDCl ): δ = 7.92 (dd, J = 8.0, 1.0 Hz, 1 H), 7.53–7.48
3
(m, 1 H), 7.34–7.22 (m, 7 H), 5.49 (s, 2 H), 4.52 (q, J = 7.2 Hz, 2 H), 1.45
(
t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl
32.3, 131.9, 131.0, 128.8, 127.7, 126.8, 124.0, 114.5, 62.3, 45.8, 14.0.
): δ = 163.6, 152.5, 149.0, 134.5, 133.2,
3
1
+
EI-MS: m/z (%) = 308 (93) [M ], 234 (42), 207 (88), 206 (100), 91 (84).
Ethyl 4-Benzyl-7-methyl-3-oxo-3,4-dihydroquinoxaline-2-carbox-
8b
ylate (2b)
Yellow solid; mp 104–105 °C; yield: 138 mg (86%).
1H NMR (400 MHz, CDCl
): δ = 7.71 (s, 1 H), 7.33–7.18 (m, 7 H), 5.46
s, 2 H), 4.51 (q, J = 7.2 Hz, 2 H), 2.38 (s, 3 H), 1.45 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl
): δ = 163.8, 152.5, 148.9, 134.7, 134.0,
33.6, 132.0, 131.1, 130.8, 128.8, 127.7, 126.9, 114.3, 62.3, 45.8, 20.4,
4.0.
3
(
3
1
1
+
EI-MS: m/z (%) = 322 (80) [M ], 248 (39), 221 (94), 220 (85), 91 (100).
Ethyl 4-Benzyl-7-methoxy-3-oxo-3,4-dihydroquinoxaline-2-car-
8b
boxylate (2c)
Yellow solid; mp 122–123 °C; yield: 135 mg (80%).
1
H NMR (400 MHz, CDCl ): δ = 7.39 (d, J = 2.8 Hz, 1 H), 7.32–7.21 (m, 6
3
H), 7.15 (dd, J = 9.2, 2.8 Hz, 1 H), 5.49 (s, 2 H), 4.53 (q, J = 7.2 Hz, 2 H),
3
.84 (s, 3 H), 1.46 (t, J = 7.2 Hz, 3 H).
13
C NMR (100 MHz, CDCl ): δ = 163.6, 156.0, 152.1, 149.1, 134.6,
3
1H and 13C NMR spectra were recorded in CDCl on a Bruker AM-400
MHz spectrometer. The chemical shifts in H NMR spectra were de-
3
1
32.7, 128.7, 127.6, 127.5, 126.8, 121.8, 115.4, 111.8, 62.3, 55.5, 45.9,
1
13.9.
termined with TMS as the internal standard (δ = 0.00 ppm). The
+
13
EI-MS: m/z (%) = 338 (85) [M ], 237 (88), 236 (71), 233 (42), 91 (100).
chemical shifts in C NMR spectra were determined based on the
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

F
Synthesis
D. Li et al.
Special Topic
Ethyl 4-Benzyl-7-fluoro-3-oxo-3,4-dihydroquinoxaline-2-carbox-
ylate (2d)
Ethyl 4-Benzyl-3-oxo-7-phenyl-3,4-dihydroquinoxaline-2-carbox-
ylate (2i)
8b
8b
Yellow solid; mp 74–75 °C; yield: 121 mg (74%).
Yellow oil; yield: 136 mg (71%).
1
H NMR (400 MHz, CDCl ): δ = 7.62–7.60 (m, 1 H), 7.32–7.23 (m, 7 H),
Rf = 0.36 (petroleum ether–EtOAc, 3:1).
3
5
.49 (s, 2 H), 4.52 (q, J = 7.2 Hz, 2 H), 1.45 (t, J = 7.2 Hz, 3 H).
1
H NMR (400 MHz, CDCl ): δ = 8.16 (s, 1 H), 7.75–7.73 (m, 1 H), 7.57–
3
13
C NMR (100 MHz, CDCl ): δ = 163.4, 158.5 (d, J = 244 Hz), 151.3 (d,
7.55 (m, 2 H), 7.42 (t, J = 7.2 Hz, 2 H), 7.36–7.25 (m, 7 H), 5.50 (s, 2 H),
3
J = 176 Hz), 134.3, 132.5 (d, J = 11 Hz), 129.92, 129.90, 128.9, 127.9,
4.53 (q, J = 7.2 Hz, 2 H), 1.46 (t, J = 7.2 Hz, 3 H).
1
26.8, 120.2 (d, J = 24 Hz), 116.3, 116.1, 116.0, 115.9, 62.5, 46.1, 14.0.
13
C NMR (100 MHz, CDCl ): δ = 163.6, 152.4, 149.3, 138.4, 137.0,
3
+
EI-MS: m/z (%) = 326 (76) [M ], 225 (83), 224 (93), 91 (100).
134.5, 132.3, 132.2, 131.1, 128.9, 128.81, 128.76, 128.7, 127.74,
127.71, 126.9, 126.6, 115.0, 62.4, 45.9, 14.0.
+
Ethyl 4-Benzyl-7-chloro-3-oxo-3,4-dihydroquinoxaline-2-carbox-
ylate (2e)
EI-MS: m/z (%) = 384 (85) [M ], 310 (42), 283 (90), 282 (90), 279 (38),
91 (100).
8b
Yellow solid; mp 120–121 °C; yield: 95 mg (56%).
1
Ethyl 4-Benzyl-6,8-dimethyl-3-oxo-3,4-dihydroquinoxaline-2-car-
boxylate (2j)
H NMR (400 MHz, CDCl ): δ = 7.91 (s, 1 H), 7.47–7.44 (m, 1 H), 7.33–
.22 (m, 6 H), 5.48 (s, 2 H), 4.52 (q, J = 7.2 Hz, 2 H), 1.46 (t, J = 7.2 Hz, 3
3
8b
7
H).
Yellow oil; yield: 129 mg (77%).
13
C NMR (100 MHz, CDCl ): δ = 163.3, 152.3, 150.3, 134.2, 132.6,
Rf = 0.29 (petroleum ether–EtOAc, 3:1).
3
1
32.3, 132.0, 130.3, 129.5, 129.0, 128.0, 126.8, 115.9, 62.6, 46.1, 14.0.
1
H NMR (400 MHz, CDCl ): δ = 7.30–7.22 (m, 5 H), 7.00 (s, 1 H), 6.91
3
+
+
EI-MS: m/z (%) = 344 (22) [M + 2], 342 (68) [M ], 243 (23), 242 (32),
41 (73), 240 (82), 91 (100).
(s, 1 H), 5.46 (s, 2 H), 4.50 (q, J = 7.2 Hz, 2 H), 2.62 (s, 3 H), 2.34 (s, 3 H),
1.44 (t, J = 7.2 Hz, 3 H).
2
13
C NMR (100 MHz, CDCl ): δ = 164.3, 152.6, 145.9, 143.2, 139.8,
3
Ethyl 4-Benzyl-7-bromo-3-oxo-3,4-dihydroquinoxaline-2-carbox-
ylate (2f)
134.9, 133.5, 129.1, 128.7, 127.5, 126.8, 112.4, 62.0, 45.8, 22.1, 17.3,
14.0.
8b
Yellow solid; mp 117–118 °C; yield: 141 mg (73%).
+
EI-MS: m/z (%) = 336 (100) [M ], 262 (88), 235 (81), 234 (62), 91 (75).
1
H NMR (400 MHz, CDCl ): δ = 8.06 (d, J = 2.4 Hz, 1 H), 7.58 (dd, J = 8.8,
3
2
1
.0 Hz, 1 H), 7.33–7.17 (m, 6 H), 5.47 (s, 2 H), 4.52 (q, J = 7.2 Hz, 2 H),
.45 (t, J = 7.2 Hz, 3 H).
Ethyl 4-Benzyl-8-methoxy-3-oxo-3,4-dihydroquinoxaline-2-car-
boxylate (2k-1)
8b
13
C NMR (100 MHz, CDCl ): δ = 163.3, 152.2, 150.2, 135.0, 134.2,
Yellow oil; yield: 90 mg (54%).
3
1
33.4, 132.8, 132.4, 129.0, 128.0, 126.8, 116.7, 116.1, 62.6, 46.1, 14.0.
Rf = 0.14 (petroleum ether–EtOAc, 3:1).
+
+
EI-MS: m/z (%) = 388 (34) [M + 2], 386 (33) [M ], 287 (36), 286 (46),
85 (45), 284 (43), 111 (30), 91 (100), 69 (37).
1
H NMR (400 MHz, CDCl ): δ = 7.44 (t, J = 8.4 Hz, 1 H), 7.31–7.23 (m, 5
3
2
H), 6.86 (d, J = 8.4 Hz, 1 H), 6.78 (d, J = 8.4 Hz, 1 H), 5.47 (s, 2 H), 4.49
(
13
q, J = 7.2 Hz, 2 H), 4.00 (s, 3 H), 1.44 (t, J = 7.2 Hz, 3 H).
Ethyl 4-Benzyl-7-iodo-3-oxo-3,4-dihydroquinoxaline-2-carboxyl-
ate (2g)
C NMR (100 MHz, CDCl ): δ = 163.6, 157.0, 152.6, 146.4, 134.8,
3
8b
1
1
34.6, 133.3, 128.7, 127.6, 126.8, 122.8, 106.6, 105.2, 62.2, 56.3, 46.2,
3.9.
Yellow solid; mp 164–165 °C; yield: 43 mg (20%).
1
H NMR (400 MHz, CDCl ): δ = 8.29 (d, J = 2.0 Hz, 1 H), 7.76 (dd, J = 9.2,
+
3
EI-MS: m/z (%) = 338 (70) [M ], 292 (57), 249 (55), 237 (62), 91 (100).
2.0 Hz, 1 H), 7.34–7.22 (m, 5 H), 7.04 (d, J = 9.2 Hz, 1 H), 5.47 (s, 2 H),
4
.52 (q, J = 7.2 Hz, 2 H), 1.46 (t, J = 7.2 Hz, 3 H).
Ethyl 4-Benzyl-6-methoxy-3-oxo-3,4-dihydroquinoxaline-2-car-
boxylate (2k-2)
13
8b
C NMR (100 MHz, CDCl ): δ = 163.3, 152.3, 149.8, 140.7, 139.6,
3
1
34.2, 133.1, 133.0, 129.1, 128.0, 126.9, 116.4, 86.8, 62.7, 46.0, 14.0.
Yellow oil; yield: 45 mg (27%).
+
EI-MS: m/z (%) = 434 (5) [M ], 249 (19), 111 (66), 110 (21), 69 (100),
Rf = 0.24 (petroleum ether–EtOAc, 3:1).
55 (47).
1
H NMR (400 MHz, CDCl ): δ = 7.85 (d, J = 8.8 Hz, 1 H), 7.34–7.27 (m, 5
3
H), 6.91 (dd, J = 8.8, 2.4 Hz, 1 H), 6.69 (d, J = 2.8 Hz, 1 H), 5.48 (s, 2 H),
Ethyl 4-Benzyl-3-oxo-7-(trifluoromethyl)-3,4-dihydroquinoxal-
ine-2-carboxylate (2h)
4.51 (q, J = 7.2 Hz, 2 H), 3.79 (s, 3 H), 1.46 (t, J = 7.2 Hz, 3 H).
8b
13
C NMR (100 MHz, CDCl ): δ = 163.9, 163.0, 153.1, 144.7, 135.4,
3
Pale yellow oil; yield: 120 mg (64%).
134.7, 132.9, 129.0, 127.9, 127.1, 127.0, 112.1, 98.5, 62.3, 55.7, 46.1,
Rf = 0.57 (petroleum ether–EtOAc, 3:1).
14.1.
EI-MS: m/z (%) = 338 (49) [M ], 292 (24), 237 (40), 221 (30), 220 (23),
1 (100).
1
H NMR (400 MHz, CDCl ): δ = 8.22 (s, 1 H), 7.75–7.72 (m, 1 H), 7.43
+
3
(d, J = 8.8 Hz, 1 H), 7.35–7.24 (m, 5 H), 5.52 (s, 2 H), 4.53 (q, J = 7.2 Hz,
9
2
H), 1.46 (t, J = 7.2 Hz, 3 H).
1
3
C NMR (100 MHz, CDCl ): δ = 163.1, 152.4, 150.6, 135.6, 134.0,
Ethyl 4-Benzyl-8-methyl-3-oxo-3,4-dihydroquinoxaline-2-carbox-
ylate (2l-1)
3
8b
1
31.4, 129.1, 128.63, 128.59, 128.55, 128.50, 128.47, 128.1, 126.9,
1
26.6, 126.3, 124.6, 121.9, 115.5, 62.7, 46.2, 14.0.
Yellow oil; yield: 84 mg (52%).
+
EI-MS: m/z (%) = 376 (63) [M ], 302 (37), 275 (85), 274 (100), 149 (42),
Rf = 0.33 (petroleum ether–EtOAc, 3:1).
91 (99).
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

G
Synthesis
D. Li et al.
Special Topic
1
+
+
H NMR (400 MHz, CDCl ): δ = 7.37 (t, J = 8.0 Hz, 1 H), 7.30–7.22 (m, 5
EI-MS: m/z (%) = 388 (48) [M + 2], 386 (49) [M ], 287 (50), 286 (55),
3
H), 7.16 (d, J = 7.2 Hz, 1 H), 7.11 (d, J = 8.8 Hz, 1 H), 5.48 (s, 2 H), 4.51
285 (52), 284 (54), 91 (100).
(q, J = 7.2 Hz, 2 H), 2.66 (s, 3 H), 1.45 (t, J = 7.2 Hz, 3 H).
1
3
C NMR (100 MHz, CDCl ): δ = 164.1, 152.5, 147.4, 140.2, 134.8,
Ethyl 4-Benzyl-8-chloro-3-oxo-3,4-dihydroquinoxaline-2-carbox-
ylate (2o-1)
3
8b
1
33.4, 132.0, 130.8, 128.8, 127.6, 126.8, 125.3, 112.4, 62.2, 45.9, 17.4,
14.0.
Yellow solid; mp 128–129 °C; yield: 118 mg (69%).
+
1
EI-MS: m/z (%) = 322 (100) [M ], 248 (60), 221 (88), 220 (76), 91 (89).
H NMR (400 MHz, CDCl ): δ = 7.42–7.41 (m, 2 H), 7.32–7.20 (m, 6 H),
3
5.50 (s, 2 H), 4.53 (q, J = 7.2 Hz, 2 H), 1.46 (t, J = 7.2 Hz, 3 H).
Ethyl 4-Benzyl-6-methyl-3-oxo-3,4-dihydroquinoxaline-2-carbox-
ylate (2l-2)
13
C NMR (100 MHz, CDCl ): δ = 163.4, 152.2, 149.4, 135.9, 134.8,
3
8b
134.2, 132.2, 128.9, 127.9, 126.8, 125.0, 113.5, 62.5, 46.2, 14.0.
Yellow oil; yield: 23 mg (14%).
+
+
EI-MS: m/z (%) = 344 (29) [M + 2], 342 (86) [M ], 268 (41), 243 (29),
Rf = 0.25 (petroleum ether–EtOAc, 3:1).
242 (41), 241 (92), 240 (92), 91 (100).
1
H NMR (400 MHz, CDCl ): δ = 7.83 (d, J = 8.4 Hz, 1 H), 7.35–7.26 (m, 5
3
H), 7.16 (d, J = 8.4 Hz, 1 H), 7.10 (s, 1 H), 5.49 (s, 2 H), 4.52 (q, J = 7.2
Hz, 2 H), 2.42 (s, 3 H), 1.46 (t, J = 7.2 Hz, 3 H).
Ethyl 4-Benzyl-6-chloro-3-oxo-3,4-dihydroquinoxaline-2-carbox-
ylate (2o-2)
23
13
Pale yellow oil; yield: 43 mg (25%).
C NMR (100 MHz, CDCl ): δ = 163.9, 152.8, 147.6, 143.8, 134.8,
3
133.5, 131.1, 130.4, 129.0, 127.8, 127.0, 125.7, 114.6, 62.4, 45.9, 22.3,
Rf = 0.25 (petroleum ether–EtOAc, 3:1).
1
4.1.
1
H NMR (400 MHz, CDCl ): δ = 7.88–7.86 (m, 1 H), 7.37–7.26 (m, 7 H),
3
+
EI-MS: m/z (%) = 322 (98) [M ], 248 (56), 221 (100), 220 (79), 217 (39),
5.45 (s, 2 H), 4.52 (q, J = 7.2 Hz, 2 H), 1.46 (t, J = 7.2 Hz, 3 H).
91 (75).
13
C NMR (100 MHz, CDCl ): δ = 163.4, 152.4, 149.0, 138.7, 134.3,
3
1
34.1, 132.4, 130.6, 129.1, 128.1, 127.0, 124.8, 114.6, 62.6, 46.2, 14.1.
Ethyl 4-Benzyl-8-isopropyl-3-oxo-3,4-dihydroquinoxaline-2-car-
+
+
EI-MS: m/z (%) = 344 (27) [M + 2], 342 (73) [M ], 268 (44), 243 (26),
42 (35), 241 (83), 240 (79), 91 (100).
8b
boxylate (2m-1) and Ethyl 4-Benzyl-6-isopropyl-3-oxo-3,4-dihy-
droquinoxaline-2-carboxylate (2m-2)8
2
b
Yellow oil; yield: 155 mg (89%).
Ethyl 4-Benzyl-3-oxo-8-(trifluoromethyl)-3,4-dihydroquinoxal-
ine-2-carboxylate (2p-1)
Rf = 0.50 (petroleum ether–EtOAc, 3:1).
8b
1
H NMR (400 MHz, CDCl ): δ = 7.85 (d, J = 8.4 Hz, 0.4 H), 7.46 (t, J = 8.4
Yellow solid; mp 75–76 °C; yield: 76 mg (40%).
3
Hz, 0.6 H), 7.31–7.22 (m, 6 H), 7.16–7.13 (m, 1 H), 5.51–5.49 (m, 2 H),
1
H NMR (400 MHz, CDCl ): δ = 7.66 (d, J = 7.2 Hz, 1 H), 7.58 (t, J = 8.0
3
4
1
.51 (q, J = 7.2 Hz, 2 H), 4.18–4.08 (m, 0.6 H), 2.99–2.89 (m, 0.4 H),
.45 (t, J = 7.2 Hz, 3 H), 1.29 (d, J = 6.8 Hz, 3.6 H), 1.19 (d, J = 7.2 Hz, 2.4
Hz, 1 H), 7.51 (d, J = 8.4 Hz, 1 H), 7.35–7.23 (m, 5 H), 5.53 (s, 2 H), 4.53
(q, J = 7.2 Hz, 2 H), 1.45 (t, J = 7.2 Hz, 3 H).
H).
13
C NMR (100 MHz, CDCl ): δ = 163.3, 152.0, 150.1, 134.2, 131.4,
3
13
C NMR (100 MHz, CDCl ): δ = 164.2, 163.8, 154.2, 152.8, 152.4,
3
1
29.1, 128.1, 126.8, 118.7, 62.6, 46.3, 14.0.
1
1
1
50.3, 147.6, 147.2, 134.9, 134.8, 133.31, 133.28, 132.3, 130.9, 130.5,
29.5, 128.73, 128.71, 128.4, 127.7, 127.6, 127.0, 126.8, 123.0, 120.9,
12.2, 112.1, 62.2, 62.0, 45.9, 45.8, 34.4, 27.1, 23.4, 23.3, 14.0.
+
+
EI-MS: m/z (%) = 376 (84) [M ], 275 (78), 274 (91), 91 (100).
Ethyl 4-Benzyl-3-oxo-6-(trifluoromethyl)-3,4-dihydroquinoxal-
ine-2-carboxylate (2p-2)
HRMS (ESI): m/z [M + Na] calcd for C21H22N O Na: 373.1523; found:
2
3
8b
373.1529.
Yellow oil; yield: 56 mg (30%).
Ethyl 4-Benzyl-8-bromo-3-oxo-3,4-dihydroquinoxaline-2-carbox-
ylate (2n-1)
R
= 0.50 (petroleum ether–EtOAc, 3:1).
f
8b
1
H NMR (400 MHz, CDCl ): δ = 8.05 (d, J = 8.4 Hz, 1 H), 7.61 (s, 1 H),
3
Yellow solid; mp 109–110 °C; yield: 120 mg (62%).
7.57 (d, J = 8.4 Hz, 1 H), 7.36–7.27 (m, 5 H), 5.52 (s, 2 H), 4.54 (q, J = 7.2
Hz, 2 H), 1.47 (t, J = 7.2 Hz, 3 H).
1
H NMR (400 MHz, CDCl ): δ = 7.60 (d, J = 7.6 Hz, 1 H), 7.35–7.21 (m, 7
3
13
H), 5.48 (s, 2 H), 4.52 (q, J = 7.2 Hz, 2 H), 1.45 (t, J = 7.2 Hz, 3 H).
C NMR (100 MHz, CDCl ): δ = 163.2, 152.3, 151.6, 134.0, 133.7,
3
1
3
133.4, 132.0, 129.2, 128.3, 127.2, 120.62, 120.59, 112.11, 112.06, 62.8,
6.3, 14.1.
EI-MS: m/z (%) = 376 (55) [M ], 275 (75), 274 (88), 111 (77), 91 (69),
9 (100).
C NMR (100 MHz, CDCl ): δ = 163.3, 152.3, 149.7, 134.7, 134.3,
3
4
1
32.5, 129.0, 128.4, 128.0, 126.9, 126.8, 114.3, 62.5, 46.3, 14.1.
+
+
+
EI-MS: m/z (%) = 388 (41) [M + 2], 386 (40) [M ], 287 (47), 286 (47),
85 (53), 284 (47), 91 (100).
6
2
Ethyl 4-Methyl-3-oxo-3,4-dihydroquinoxaline-2-carboxylate
(2q)
Ethyl 4-Benzyl-6-bromo-3-oxo-3,4-dihydroquinoxaline-2-carbox-
ylate (2n-2)
8b,23
8b
Yellow oil; yield: 71 mg (61%).
Pale yellow solid; mp 142–143 °C; yield: 29 mg (15%).
1
R
= 0.40 (petroleum ether–EtOAc, 3:1).
f
H NMR (400 MHz, CDCl ): δ = 7.78 (d, J = 8.8 Hz, 1 H), 7.48–7.44 (m, 2
3
1
H), 7.37–7.26 (m, 5 H), 5.45 (s, 2 H), 4.52 (q, J = 7.2 Hz, 2 H), 1.45 (t, J =
H NMR (400 MHz, CDCl ): δ = 7.95–7.93 (m, 1 H), 7.69–7.64 (m, 1 H),
3
7.2 Hz, 3 H).
7.42–7.35 (m, 2 H), 4.51 (q, J = 7.2 Hz, 2 H), 3.73 (s, 3 H), 1.45 (t, J = 7.2
1
3
Hz, 3 H).
C NMR (100 MHz, CDCl ): δ = 163.4, 152.3, 149.2, 134.4, 134.1,
3
13
1
32.4, 131.0, 129.1, 128.1, 127.7, 127.0, 117.6, 62.7, 46.2, 14.1.
C NMR (100 MHz, CDCl ): δ = 163.7, 152.5, 149.0, 134.0, 132.4,
3
131.8, 131.1, 124.1, 113.8, 62.4, 29.1, 14.0.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

H
Synthesis
D. Li et al.
Special Topic
+
1
EI-MS: m/z (%) = 232 (81) [M ], 188 (27), 160 (100), 159 (44), 132 (45),
31 (52).
H NMR (400 MHz, CDCl ): δ = 7.97–7.95 (m, 0.4 H), 7.62–7.59 (m, 1.2
3
1
H), 7.56–7.53 (m, 0.6 H), 7.47–7.43 (m, 0.9 H), 7.38–7.33 (m, 0.6 H),
.31–7.29 (m, 1.4 H), 7.22–7.20 (m, 0.8 H), 7.11–7.06 (m, 1.3 H), 6.79
(dd, J = 8.4, 0.8 Hz, 0.4 H), 6.66 (d, J = 9.2 Hz, 0.6 H), 4.50 (qd, J = 7.2,
.2 Hz, 2 H), 3.88 (s, 1.2 H), 3.86 (s, 1.8 H), 1.43 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl
): δ = 163.6, 160.2, 156.3, 152.4, 151.8,
49.9, 149.7, 135.2, 135.0, 132.4, 131.9, 131.7, 130.6, 130.2, 129.6,
7
Ethyl 4-Ethyl-3-oxo-3,4-dihydroquinoxaline-2-carboxylate (2r)8b,24
1
White solid; mp 74–75 °C; yield: 82 mg (67%).
1
3
H NMR (400 MHz, CDCl ): δ = 7.93 (d, J = 8.0 Hz, 1 H), 7.69–7.65 (m, 1
H), 7.40–7.35 (m, 2 H), 4.52 (q, J = 7.2 Hz, 2 H), 4.34 (q, J = 7.2 Hz, 2 H),
.46 (t, J = 7.2 Hz, 3 H), 1.40 (t, J = 7.2 Hz, 3 H).
3
1
1
6
29.2, 129.0, 128.0, 127.2, 124.1, 121.7, 116.5, 115.6, 115.4, 111.3,
2.4, 55.7, 55.5, 14.0.
1
13
C NMR (100 MHz, CDCl ): δ = 163.8, 152.0, 149.0, 133.0, 132.4,
32.1, 131.4, 123.9, 113.6, 62.4, 37.5, 14.0, 12.2.
3
+
EI-MS: m/z (%) = 324 (100) [M ], 252 (47), 224 (42), 223 (83), 209 (38).
1
+
EI-MS: m/z (%) = 246 (100) [M ], 200 (66), 174 (56), 172 (58), 146 (64),
Ethyl 7-Methyl-3-oxo-4-phenyl-3,4-dihydroquinoxaline-2-carbox-
118 (63).
8b
ylate (2w-1) and Ethyl 3-Oxo-4-(p-tolyl)-3,4-dihydroquinoxal-
24
ine-2-carboxylate (2w-2)
Ethyl 3-Oxo-4-phenyl-3,4-dihydroquinoxaline-2-carboxylate
Yellow oil; yield: 126 mg (82%).
8b,24
(2s)
Rf = 0.25 (petroleum ether–EtOAc, 3:1).
Yellow oil; yield: 122 mg (83%).
1
H NMR (400 MHz, CDCl ): δ = 7.97 (d, J = 8.0 Hz, 0.4 H), 7.77 (s, 0.6
3
Rf = 0.36 (petroleum ether–EtOAc, 3:1).
H), 7.61–7.53 (m, 1.6 H), 7.45–7.16 (m, 4.5 H), 6.77 (d, J = 8.8 Hz, 0.4
H), 6.63 (d, J = 8.8 Hz, 0.6 H), 4.48 (q, J = 7.2 Hz, 2 H), 2.46 (s, 1.2 H),
1
H NMR (400 MHz, CDCl ): δ = 7.97 (d, J = 8.0 Hz, 1 H), 7.63–7.53 (m, 3
3
H), 7.44 (t, J = 8.0 Hz, 1 H), 7.37–7.29 (m, 3 H), 6.73 (d, J = 8.0 Hz, 1 H),
2
.42 (s, 1.8 H), 1.42 (t, J = 7.2 Hz, 3 H).
4.50 (q, J = 7.2 Hz, 2 H), 1.43 (t, J = 7.2 Hz, 3 H).
13
C NMR (100 MHz, CDCl ): δ = 163.6, 163.5, 152.1, 151.9, 149.6,
3
13
C NMR (100 MHz, CDCl ): δ = 163.5, 152.0, 149.7, 134.8, 134.7,
3
149.5, 139.6, 134.9, 134.8, 134.1, 133.2, 132.5, 132.1, 131.8, 131.6,
31.5, 130.7, 130.4, 130.1, 130.0, 129.4, 127.9, 127.6, 124.0, 115.6,
131.9, 131.6, 130.6, 130.2, 129.6, 128.0, 124.2, 115.5, 62.3, 14.0.
1
+
EI-MS: m/z (%) = 294 (46) [M ], 222 (46), 194 (28), 91 (100).
115.2, 62.21, 62.18, 21.1, 20.4, 13.9.
+
EI-MS: m/z (%) = 308 (55) [M ], 236 (43), 208 (35), 207 (100).
Ethyl 3-Oxo-6,7-dihydro-3H,5H-pyrido[1,2,3-de]quinoxaline-2-
carboxylate (2t)
8
a,b
Ethyl 7-Bromo-3-oxo-4-phenyl-3,4-dihydroquinoxaline-2-carbox-
8b
Yellow solid; mp 146–147 °C; yield: 88 mg (68%).
ylate (2x-1) and Ethyl 4-(4-Bromophenyl)-3-oxo-3,4-dihydroqui-
8b
1
noxaline-2-carboxylate (2x-2)
H NMR (400 MHz, CDCl ): δ = 7.76 (d, J = 8.0 Hz, 1 H), 7.41–7.39 (m, 1
3
H), 7.27 (t, J = 8.0 Hz, 1 H), 4.51 (q, J = 7.2 Hz, 2 H), 4.16 (t, J = 6.0 Hz, 2
H), 3.00 (t, J = 6.0 Hz, 2 H), 2.18–2.12 (m, 2 H), 1.45 (t, J = 7.2 Hz, 3 H).
Yellow oil; yield: 95 mg (51%).
Rf = 0.42 (petroleum ether–EtOAc, 3:1).
13
C NMR (100 MHz, CDCl ): δ = 163.8, 151.8, 148.3, 131.6, 131.3,
1
3
H NMR (400 MHz, CDCl ): δ = 8.12–8.11 (m, 0.4 H), 7.98 (d, J = 8.0 Hz,
3
130.4, 128.6, 124.7, 123.5, 62.2, 41.8, 26.2, 20.0, 14.0.
0.6 H), 7.75 (d, J = 7.6 Hz, 1 H), 7.64–7.55 (m, 1.2 H), 7.52–7.44 (m, 1
+
EI-MS: m/z (%) = 258 (73) [M ], 186 (100), 185 (29), 158 (53), 157 (58).
H), 7.38 (t, J = 7.6 Hz, 0.6 H), 7.28 (d, J = 7.6 Hz, 1 H), 7.20 (d, J = 8.0 Hz,
1
7
.2 H), 6.74 (d, J = 8.0 Hz, 0.6 H), 6.62 (d, J = 8.8 Hz, 0.4 H), 4.50 (q, J =
.2 Hz, 2 H), 1.43 (t, J = 7.2 Hz, 3 H).
Ethyl 4-Benzyl-3-oxo-3,4-dihydrobenzo[f]quinoxaline-2-carboxyl-
ate (2u)
8b
13
C NMR (100 MHz, CDCl ): δ = 163.4, 163.2, 152.0, 151.8, 151.0,
3
Yellow solid; mp 128–129 °C; yield: 72 mg (40%).
149.6, 134.7, 134.5, 133.9, 133.9, 133.6, 132.9, 132.4, 132.2, 131.7,
130.9, 130.4, 129.9, 127.9, 124.5, 123.8, 117.1, 116.8, 115.3, 62.6, 62.5,
1
H NMR (400 MHz, CDCl ): δ = 8.96 (d, J = 8.4 Hz, 1 H), 7.95 (d, J = 9.2
3
14.1.
Hz, 1 H), 7.82 (d, J = 8.0 Hz, 1 H), 7.72 (t, J = 8.0 Hz, 1 H), 7.60–7.56 (m,
+
+
1
H), 7.42 (d, J = 9.2 Hz, 1 H), 7.34–7.26 (m, 5 H), 5.65 (s, 2 H), 4.57 (q,
EI-MS: m/z (%) = 374 (29) [M + 2], 372 (29) [M ], 294 (51), 273 (55),
J = 7.2 Hz, 2 H), 1.50 (t, J = 7.2 Hz, 3 H).
271 (54), 222 (42), 193 (100), 192 (43).
13
C NMR (100 MHz, CDCl ): δ = 164.2, 153.2, 146.2, 134.8, 134.2,
3
Ethyl 4-Benzyl-3,8-dioxo-1,4-diazaspiro[4.5]deca-1,6,9-triene-2-
carboxylate (4g)
1
32.2, 131.4, 129.8, 129.0, 128.7, 127.9, 127.7, 127.4, 126.9, 126.8,
8a
123.4, 113.9, 62.3, 46.4, 14.2.
+
Pale yellow oil; yield: 104 mg (64%).
HRMS (ESI): m/z [M + Na] calcd for C22H18N O Na: 381.1210; found:
2
3
381.1205.
Rf = 0.18 (petroleum ether–EtOAc, 3:1).
1
H NMR (400 MHz, CDCl ): δ = 7.29–7.27 (m, 3 H), 7.21–7.20 (m, 2 H),
3
Ethyl 7-Methoxy-3-oxo-4-phenyl-3,4-dihydroquinoxaline-2-car-
6.36 (d, J = 10.0 Hz, 2 H), 6.03 (d, J = 10.0 Hz, 2 H), 4.55 (s, 2 H), 4.48 (q,
J = 7.2 Hz, 2 H), 1.43 (t, J = 7.2 Hz, 3 H).
8b
boxylate (2v-1) and Ethyl 4-(4-Methoxyphenyl)-3-oxo-3,4-dihy-
8b
droquinoxaline-2-carboxylate (2v-2)
13
C NMR (100 MHz, CDCl ): δ = 183.3, 162.1, 160.1, 159.5, 141.0,
3
Yellow oil; yield: 105 mg (65%).
135.2, 132.5, 128.8, 128.7, 128.4, 81.4, 63.1, 45.1, 13.9.
Rf = 0.20 (petroleum ether–EtOAc, 3:1).
+
EI-MS: m/z (%) = 324 (32) [M ], 252 (32), 223 (100), 209 (53).
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

I
Synthesis
D. Li et al.
Special Topic
Funding Information
(9) For similar observations in the case of reactions under copper
catalysis, see: Chiba, S.; Zhang, L.; Lee, J.-Y. J. Am. Chem. Soc.
The authors thank the National Natural Science Foundation of China
2010, 132, 7266.
(No. 21372108) for financial support
N
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atuarl
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10) Reck, R.; Jochims, J. C. Chem. Ber. 1982, 115, 1494.
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Supporting Information
(
(
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588462.
Radicals in Organic Synthesis;2Vo.
l
Renaud, P.; Sibi, M. P., Eds.; Wiley-
S portioIgnfrm oaitn
u
p
S
u
p
p
ortioIgnfrm oaitn
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(
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©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I