Sulfur-mediated annulation of 1,2-phenylenediamines towards benzofuro- A nd benzothieno-quinoxalines

Article abstract of DOI:10.1039/d0ob00887g

We report a method for condensation between ortho-phenylenediamines and ortho-hydroxyacetophenones to afford benzofuroquinoxalines. The reactions proceeded in the presence of an elemental sulfur mediator, DABCO base, and DMSO solvent. Functionalities such as nitrile, ester, and halogen groups were compatible. The conditions could be applicable for the synthesis of benzothienoquinoxalines from ortho-chloroacetophenones.

Full text of DOI:10.1039/d0ob00887g

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Sulfur-mediated annulation of 1,2-
phenylenediamines towards benzofuro- and
Cite this: DOI: 10.1039/d0ob00887g
benzothieno-quinoxalines†
Loan T. Tran,‡a,b Tuan H. Ho,
‡
a,b Nhu T. A. Phan,a,b Tung T. Nguyen
*
a,b and
a,b
Nam T. S. Phan
*
We report a method for condensation between ortho-phenylenediamines and ortho-hydroxyacetophe-
nones to afford benzofuroquinoxalines. The reactions proceeded in the presence of an elemental sulfur
mediator, DABCO base, and DMSO solvent. Functionalities such as nitrile, ester, and halogen groups were
compatible. The conditions could be applicable for the synthesis of benzothienoquinoxalines from ortho-
chloroacetophenones.
Received 29th April 2020,
Accepted 1st July 2020
DOI: 10.1039/d0ob00887g
rsc.li/obc
external bases and solvents. The addition of a strong acid such
as trifluoroacetic acid could diversify the outcome of the reac-
tions, furnishing tetraamination products.4b We envisaged
Introduction
Quinoxaline-embedded polyaromatics find uses in functional
materials and bio-related studies (Scheme 1).1 Nevertheless,
synthetic methodologies for these highly condensed molecules
are exceedingly rare. Most of the known examples are of indo-
loquinoxalines.2 Only a few methods for the synthesis of furan-
and thiophene-fused compounds were reported. Zanardi and
co-workers presented a radical annulation of 2-cyanoaryl diazo-
nium salts with isothiocyanates to afford benzothienoquinoxa-
lines.3a In one example, benzofuroquinoxaline was obtained in
a moderate yield after a two-step condensation/substitution of
1,2-phenylenediamine and a chloro-substituted α-ketothioester.3b
The development of a general method for the synthesis of
these furan- and thiophene-fused quinoxalines is thus in
demand.
Elemental sulfur mediated annulation of ortho-phenylene-
diamines and C–H bonds has been recently used as a direct
method to obtain quinoxalines and other N,N-polyaromatics.4
Since the cheap, abundant elemental sulfur has been known
for the functionalization of C–H bonds α to CvO groups,5 the
element was previously used to facilitate the coupling of
cycloalkanones with diamines, affording tricyclic, substituted
quinoxalines.4a The reactions did not require the use of any
that if the quinoxaline ring is formed in the presence of a prox-
imal nucleophile such as phenoxide or thiolate, intra-
molecular cyclization would be viable, thus affording another
fused ring. Such a design is observed in ortho-hydroxyaceto-
phenones or ortho-haloacetophenones. It should be noted that
although oxidation of α sp3 C–H bonds in ketones with
elemental sulfur is well precedented, certain problems are still
unsolved. Firstly, methyl C–H bonds in acetophenones are less
reactive than those in cycloalkanones.6 Most of the known
methods often suffer from the use of prefunctionalized oxime
esters.7 Secondly, sterically hindered, ortho-substituted aceto-
phenones are sometimes incompetent substrates in elemental-
sulfur-promoted transformations.5b Herein we report our
attempts to obtain benzofuroquinoxalines via a coupling of
ortho-phenylenediamines and ortho-hydroxyacetophenones.
The reactions proceeded in the presence of an elemental
sulfur mediator, DABCO base, and DMSO solvent. Later, the
same conditions were used to annulate ortho-chloroacetophe-
nones with diamines, thus furnishing benzothienoquinoxa-
lines presumably after an SNAr-type sulfuration.
aFaculty of Chemical Engineering, Ho Chi Minh City University of Technology
(HCMUT), 268 Ly Thuong Kiet, District 10, Ho Chi Minh City, Vietnam.
E-mail: tungtn@hcmut.edu.vn, ptsnam@hcmut.edu.vn
bVietnam National University Ho Chi Minh City, Linh Trung Ward, Thu Duc District,
Ho Chi Minh City, Vietnam
†Electronic supplementary information (ESI) available: Details of optimization,
experimental procedures, and characterization of unknown compounds. See
DOI: 10.1039/d0ob00887g
‡These authors contributed equally to this work.
Scheme 1 Quinoxaline-fused polyaromatics.
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Results and discussion
We started our study by focusing on the reaction of 1,2-
phenylenediamine 1a and 2′-hydroxyacetophenone 2a in the
presence of elemental sulfur. Optimization was carried out
with respect to the solvent and base. The results are presented
in Table 1. The annulation was tolerant of most bases, includ-
ing inorganic and organic bases (entries 1–6). Similar to our
previous studies,8 DABCO was the most active base, affording
97% yield of benzofuroquinoxaline 3aa (entry 4). Decreasing
the amount of elemental sulfur resulted in significant drops of
yields (entries 7–9). Meanwhile, performing the annulation in
the presence of 3 equivalents of elemental sulfur furnished a
quantitative yield of 3aa (entry 10). Omitting the base had a
negative impact on the reaction (entry 11). The reaction could
be set up under air without a prominent loss of yield (entry
12). Solvents other than DMSO were not effective for the annu-
lation (entries 13 and 14). A solvent-free reaction afforded 3aa
in 24% yield (entry 15). Decreasing the amount of DMSO
afforded 3aa in a quantitative yield (entry 16). Lastly, the
kinetic study indicated that the annulation could be per-
formed within 0.5 h (Scheme 2).
Scheme 2 Kinetic profile of the annulation of 1a and 2a.
The scope of 1,2-phenylenediamines was next studied. The
results are presented in Scheme 3. It should be noted that tol-
erance of functionalities has not been mentioned in the pre-
Table 1 Studies of reaction conditionsa
Scheme 3 Scope of 1,2-phenylenediamines. Reaction conditions:
Diamines (0.25 mmol), 2a (1.05 equiv.), elemental sulfur (0.75 mmol,
32 g mol−1), DABCO (1.5 equiv.), DMSO (1 mmol), 120 °C, 30 min. Yields
Sulfur amount
(equiv.)
Yield of
3aa (%)
are isolated yields. a Obtained as
a 7 : 3 regioisomeric product.
Entry
Base
Solvent
b Obtained as a 94 : 6 regioisomeric product. c Obtained as a 4 : 1 regioi-
someric product. d Obtained as a 2 : 1 regioisomeric product. e The nitro
group was reduced after the reaction.
1
2
3
4
5
6
7
8
NaOH
KOH
K3PO4
DABCO
MM
DMPP
DABCO
DABCO
DABCO
DABCO
—
DABCO
DABCO
DABCO
DABCO
DABCO
2
2
2
2
2
2
1
0.5
0.25
3
3
3
3
3
3
3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
CH3CN
Dioxane
—
74
69
69
97
70
81
92
86
40
Quant.
61
Quant.
22
14
vious sulfur-mediated annulation of 1,2-phenylediamines.6a,b
Using our standard conditions, the unsubstituted benzofuro-
quinoxaline 3aa was isolated in 97% yield. Unsymmetrical dia-
mines afforded the products as mixtures of isomers (at posi-
tions x and y, Scheme 3). Either electron-rich (3ba + 3b′a, 3ca +
3c′a) or electron-poor (3da + 3d′a, 3ea, 3fa + 3f′a) diamines
were competent substrates. Cyano (3ea) and ester (3fa + 3f′a)
groups remained intact after annulation. Reduction of the
9
10
11
12b
13b
14b
15b
16b,c
24
Quant.
Dioxane
a 1a (0.25 mmol), 2a (0.5 mmol), elemental sulfur (32 g mol−1), base nitro functionality was observed, affording amino-substituted
(1.5 equiv.), solvent (0.5 mL) under argon at 120 °C for 16 h. Yields of
benzofuroquinoxaline 3ga in a moderate yield. Its photo-
3aa are GC yields using a diphenyl ether internal standard. b Under air.
c DMSO (1 mmol). Abbreviations: MM = N-methylmorpholine, DMPP =
N,N-dimethylpiperazine, quant. = quantitative.
physical properties were somewhat different from those of
other derivatives.9 Disubstituted 1,2-phenylenediamines were
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Scheme 5 Synthesis of benzothienoquinoxalines. Reaction conditions:
Diamines (1.5 equiv.), 2’-haloacetophenones (0.25 mmol), elemental
sulfur (0.5 mmol, 32 g mol−1), DABCO (0.75 mmol), DMSO (0.5 mmol),
120 °C, 2 h. Yields are isolated yields. a Obtained as 8 : 1 mixtures of
regioisomeric products. b Obtained as a 5 : 1 mixture of regioisomeric
products.
Scheme 4 Scope of 2’-hydroxyacetophenones. Reaction conditions: 1a
(0.25 mmol), 2b–2j (1.05 equiv.), elemental sulfur (0.75 mmol, 32 g
mol−1), DABCO (1.5 equiv.), DMSO (1 mmol), 120 °C, 30 min. Yields are
isolated yields.
also compatible with the conditions (3ha, 3ia + 3i′a, 3ja). A
hindered diamine afforded the products (3ia + 3i′a) in 33%
yield, implying the steric effect on annulation. Polycyclic ben-
zofuroquinoxaline 3ja was obtained in a moderate yield when
naphthylene-1,2-diamine was used.
The reaction scope with respect to 2′-hydroxyacetophenones
is presented in Scheme 4. Halo-substituted substrates were
competent substrates apart from 2h, furnishing the benzofuro-
quinoxalines in good yields (3ab, 3ac, 3ad). The reaction con-
ditions were tolerant of reducing-sensitive functionalities such
as the CN group (3ae). Uses of electron-rich 2′-hydroxyaceto-
Scheme 6 Annulation of 1,2-phenylenediamine and 2’-aminoaceto-
phenones. Reaction conditions: 1a (0.25 mmol), 6a or 6b (0.5 mmol),
phenones were feasible (3af, 3ag). An acetyl naphthol success- elemental sulfur (1.05 equiv.), DABCO (1.5 equiv.), DMSO (1 mmol),
120 °C, 30 min. Yields are isolated yields.
fully coupled with 1,2-phenylenediamine to afford a pentacyc-
lic furoquinoxaline in 51% yield (3ai). A hindered, 3′-substi-
tuted 2′-hydroxyacetophenone could also be used to afford the
benzofuroquinoxaline in a moderate yield (3aj).
Indoloquinoxalines were the products when phenylenedia-
The standard conditions were suitable for the synthesis of mines coupled with 2′-aminoacetophenones such as 6a and
benzothienoquinoxalines when 2′-chloroacetophenones were 6b. Thus, N-benzyl indoloquinoxaline 7aa was isolated in 78%
used to couple with 1,2-phenylenediamines. We proposed that yield (Scheme 6). Unprotected 2′-aminoacetophenone was also
an intramolecularly nucleophilic sulfuration would forge an a competent substrate, affording the product 7ab in 67% yield.
annulated thiophene ring.10 The scope of the substrates is pre- Attempts to couple aliphatic diamines were also carried out
sented in Scheme 5. A high yield of unsubstituted benzothie- (Scheme 7). Substituted piperazines (8, 9) were obtained in low
noquinoxaline 5aa was obtained when 2′-chloroacetophenone yields from the annulation of ethylenediamine.
was used. ortho-Bromo- and ortho-nitroacetophenones could
The method was somewhat easy to scale up. Such examples
be used, albeit affording 5aa in lower yields. Annulation of for the synthesis of benzofuroquinoxalines are shown in
other 1,2-phenylenediamines with 2′-chloroacetophenone was Scheme 8. The yields were comparable with those obtained in
viable. Although unsymmetrical diamines afforded regioiso- small scale runs.
meric benzothienoquinoxalines, the ratios were acceptable
At this moment, we propose a possible mechanism as
(5ba, 5fa, 5la). The derivatives of 2′-chloroacetophenones were shown in Scheme 9. Condensation of diamine 1a and the
compatible with the reaction conditions, affording substituted ketone functionality would afford imine 10. The control experi-
benzothienoquinoxalines in moderate to good yields (5ab, ment showed a significant amount of the imine when DABCO
5ac). A 6,6,5,5-tetracyclic heterocycle was obtained in a small was used at elevated temperature. Tautomerization followed by
quantity (5ad).
sulfuration of α C–H bonds gave Willgerodt–Kindler type imi-
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was envisaged that elemental sulfur was the major oxidant. A
synergistic effect of elemental sulfur and DMSO as co-oxidants
is known.4b When 2′-methoxyacetophenone was reacted with
1a under standard conditions, a mixture of quinoxalines (13a,
14a) was obtained (eqn (1)). It should be noted that 2-halosub-
stituted intermediate 13 was crucial for the formation of ben-
zothienoquinoxaline 5aa, since intermolecular sulfuration of
chloro-substituted quinoxaline 15 was not observed (eqn (2)),
thus supporting the suggested mechanism. Meanwhile, benzo-
furoquinoxaline 5aa or indoloquinoxaline 7aa could be
obtained by an intramolecular cyclization of phenol (X = OH)
or aniline (X = NHR) functionalities in intermediates 14.
Scheme 7 Annulation of ethylenediamine. Reaction conditions:
Ethylenediamine (0.25 mmol), 6a or 4a (0.5 mmol), elemental sulfur (2.5
equiv.), DABCO (1.5 equiv.), DMSO (1 mmol), 120 °C, 30 min. Yields are
isolated yields.
Conclusions
In conclusion, we have developed a method for the sulfur-
mediated synthesis of benzofuroquinoxalines, benzothieno-
quinoxalines, and indoloquinoxalines from annulation of 1,2-
phenylenediamines. The use of functional groups such as
halogens, esters, and nitriles was compatible with the reaction
conditions. Early mechanistic studies proposed an oxidative
sulfuration of α C–H bonds in ortho-substituted acetophe-
nones followed by intramolecular addition of amine to afford
quinoxalines. Ongoing projects include the expansion of the
reaction scope.
Scheme 8 Gram-scale reactions.
Experimental
Materials and instrumentation
All reagents and starting materials were obtained commercially
and used as received without any further purification unless
otherwise noted. Gas chromatographic (GC) analyses were
performed using a Shimadzu GC 2010-Plus equipped with a
flame ionization detector (FID) and an SPB-5 column (length =
30 m, inner diameter = 0.25 mm, and film thickness =
0.25 μm). GC-MS analyses were performed on a Shimadzu
GCMS-QP2010Ultra with a ZB-5MS column (length = 30 m,
inner diameter = 0.25 mm, and film thickness = 0.25 μm).
1H NMR and 13C NMR were performed on Bruker AV 500 spec-
trometers. Chemical shifts were reported in ppm and refer-
enced to the residual peak for CDCl3 (δ = 7.26 ppm for
1H NMR and δ = 77.2 ppm for 13C NMR) or DMSO-d6 (δ =
2.50 ppm for 1H NMR and δ = 39.5 ppm for 13C NMR).
Splitting was reported with the following symbols: s = singlet,
bs = broad singlet, d = doublet, t = triplet, q = quartet, td =
triplet of doublets, dd = doublet of doublets, ddd = doublet of
doublets of doublets, and m = multiplet. Coupling constants
(J) were reported in hertz. HR-MS spectra were recorded
using an Agilent HPLC 1200 Series coupled to a Bruker
micrOTOF-QII. Compound 15 was synthesized following a
known procedure.11
Scheme 9 Mechanistic consideration.
nothioaldehyde 11. A rapid 6-exo-trig cyclization would afford a
hemi thioaminal 12. Oxidation of 12 furnished thiol-derived
General procedure
quinoxaline 13 or 14. Since a low yield (24% for 3aa) of the In a typical experiment, a vial equipped with a magnetic stir
annulation product was obtained when DMSO was omitted, it bar was charged with o-phenylenediamine 1a (0.25 mmol),
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2′-hydroxyacetophenone 2a (0.5 mmol), elemental sulfur xyquinoxaline was also observed. Rf = 0.40 (major) and 0.30
(32 mg mmol−1), DABCO, and DMSO. The vial was placed on a (minor) (hexanes/ethyl acetate 20 : 1). 1H NMR (500 MHz,
pre-heated oil bath at 120 °C, and then stirred for 30 min. CDCl3) δ 8.57 (minor isomer, s, 1H), 8.42 (major isomer, s,
Upon the completion of the reaction, ethyl acetate (5 mL) and 1H), 8.36 (major isomer, d, J = 8.8 Hz, 1H), 8.32 (major isomer,
brine (5 mL) were added to quench the reaction. The organic d, J = 8 Hz, 1H), 8.31 (minor isomer, d, J = 7.5 Hz, 1H), 8.23
phase was then extracted with ethyl acetate (3 × 5 mL), dried (minor isomer, d, J = 8.7 Hz, 1H), 7.97–7.93 (overlapping of
over anhydrous Na2SO4, filtered, and purified by column two isomers, 1H), 7.70–7.67 (overlapping of two isomers, 1H),
chromatography using an eluent of hexanes/EtOAc.
7.54–7.51 (overlapping of two isomers, 1H). 13C NMR
Benzofuro[2,3-b]quinoxaline (3aa). After column chromato- (126 MHz, CDCl3, possible peaks are listed) δ 158.9, 158.8,
graphy (hexanes/ethyl acetate 100 : 1 to 5 : 1), 53.2 mg (97%) of 156.6, 156.3, 142.6, 142.3, 142.1, 141.1, 140.1, 138.8, 133.3,
a yellow-white solid was obtained. Rf = 0.31 (hexanes/ethyl 133.2, 131.2 (q, J = 33.0 Hz), 130.3, 129.8, 127.1 (minor isomer,
1
acetate 12 : 1). H NMR (500 MHz, CDCl3) δ 8.35 (d, J = 7.7 Hz, q, J = 4.4 Hz), 126.6 (major isomer, q, J = 4.4 Hz), 125.3
1H), 8.33–8.29 (m, 1H), 8.19–8.15 (m, 1H), 7.84–7.78 (m, 2H), (minor isomer, q, J = 2.5 Hz), 124.8, 124.0 (major isomer,
7.74–7.70 (m, 1H), 7.68 (d, J = 8.1 Hz, 1H), 7.54–7.49 (m, 1H). q, J = 3.1 Hz), 123.3, 122.7, 120.7. HR-MS (ESI) calcd for
13C NMR (126 MHz, CDCl3) δ 158.6, 156.0, 141.3, 140.7, 139.9, C15H8F3N2O+ [M + H]+: 289.0583, found 289.0584.
132.5, 129.9, 129.3, 128.8, 128.4, 124.6, 123.1, 121.4, 112.9.
HR-MS (ESI) calcd for C14H9N2O+ [M + H]+: 221.0709, found column chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1),
221.0706. 57.4 mg (94% yield) of a yellow-brown solid was obtained. Rf =
Benzofuro[2,3-b]quinoxaline-8-carbonitrile (3ea). After
9-Methylbenzofuro[2,3-b]quinoxaline and 8-methyl- 0.34 (hexanes/ethyl acetate 3 : 1). 1H NMR (500 MHz, DMSO-d6)
benzofuro[2,3-b]quinoxaline (3ba + 3b′a). After column chrom- δ 8.66 (d, J = 1.7 Hz, 1H), 8.42 (d, J = 8.6 Hz, 1H), 8.37 (d, J =
atography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 50.4 mg 7.6 Hz, 1H), 8.13 (dd, J = 8.6, 1.8 Hz, 1H), 7.93–7.87 (m, 2H),
(86% yield) of a yellow-white solid (as a 7 : 3 regioisomeric 7.67–7.60 (m, 1H). 13C NMR (126 MHz, DMSO-d6) δ 158.4,
product) was obtained. Rf = 0.36 (major) and 0.33 (minor) 155.8, 142.7, 142.0, 138.1, 133.7, 133.5, 130.1, 129.0, 124.8,
(hexanes/ethyl acetate 9 : 1). 1H NMR (500 MHz, CDCl3) 122.9, 119.9, 117.7, 112.6, 111.6. HR-MS (ESI) calcd for
δ 8.31–8.29 (overlapping of two isomers, 1H), 8.15 (minor C15H8N3O+ [M + H]+: 246.0662, found 246.0653.
isomer, dd, J = 8.5, 2.0 Hz, 1H), 8.04 (major isomer, s, 0.7H),
Ethyl benzofuro[2,3-b]quinoxaline-8-carboxylate and ethyl
8.02 (major isomer, dd, J = 8.5, 2.0 Hz, 1H), 7.90 (minor benzofuro[2,3-b]quinoxaline-9-carboxylate (3fa + 3f′a). After
isomer, s, 1H), 7.71–7.58 (overlapping of two isomers, 3H), column chromatography (2% triethylamine in hexanes/ethyl
7.49–7.47 (overlapping of two isomers, 1H), 2.62 (overlapping acetate 100 : 1 to 5 : 1), 30.5 mg (42% yield) of a white solid (as
of two isomers, 3H). 13C NMR (126 MHz, CDCl3, possible a 2 : 1 regioisomeric product) was obtained. Rf = 0.36 (major)
peaks are listed) δ 158.5, 158.3, 156.1, 155.7, 141.3, 140.6, and 0.33 (minor) (hexanes/ethyl acetate 9 : 1). 1H NMR
140.3, 140.0, 139.76, 139.66, 138.8, 138.2, 132.1, 132.0, 130.7, (500 MHz, CDCl3) δ 8.98 (minor isomer, d, J = 1.8 Hz, 1H), 8.84
128.7, 128.23, 123.19, 127.8, 124.48, 124.45, 122.9, 122.8, (major isomer, d, J = 1.8 Hz, 1H), 8.40–8.34 (overlapping of two
121.53, 121.49, 112.82, 112.79, 22.0, 21.8. HR-MS (ESI) calcd isomers, 1H), 8.33–8.31 (overlapping of two isomers, 1H),
for C15H11N2O+ [M + H]+: 235.0866, found 235.0866.
8.29 (major isomer, d, J = 8.7 Hz, 1H), 8.16 (minor isomer, d,
9-Methoxybenzofuro[2,3-b]quinoxaline and 8-methoxybenzo- J = 8.7 Hz, 1H), 7.76–7.70 (overlapping of two isomers, 1H),
furo[2,3-b]quinoxaline (3ca + 3c′a). After column chromato- 7.76–7.67 (overlapping of two isomers, 1H), 7.53–7.50 (overlap-
graphy (hexanes/ethyl acetate 100 : 1 to 5 : 1), 30.7 mg (49% ping of two isomers, 1H), 4.50–4.46 (overlapping of two
yield) of a yellow-white solid (as a 96 : 4 regioisomeric product) isomers, 2H), 1.48–1.45 (overlapping of two isomers, 3H). 13C
was obtained. Rf (major) = 0.34 (hexanes/ethyl acetate 5 : 1). NMR (126 MHz, CDCl3, possible peaks are listed) δ 165.98,
1H NMR (500 MHz, CDCl3) δ 8.31 (major isomer, dd, J = 7.5, 165.94, 159.1, 158.8, 156.7, 156.3, 143.4, 142.4, 139.1, 133.3,
0.5 Hz, 1H), 8.29 (minor isomer, dd, J = 7.5, 0.5 Hz, 1H), 8.15 133.0, 131.7, 131.3, 131.2, 130.3, 129.45, 129.38, 128.9, 128.1,
(minor isomer, d, J = 9.2 Hz, 1H), 8.03 (major isomer, d, J = 9.2 124.9, 124.8, 123.4, 123.2, 121.0, 113.0, 112.9, 61.73, 61.68,
+
Hz, 1H), 7.72–7.67 (overlapping of two isomers, 2H), 7.59 (over- 14.5. HR-MS (ESI) calcd for C17H13N2O3 [M + H]+: 293.0921,
lapping of two isomers, for the major isomer, d, J = 2.5 Hz, found 293.0912.
1H), 7.50–7.45 (overlapping of two isomers, 2H), 4.00 (overlap-
Benzofuro[2,3-b]quinoxalin-8-amine (3ga). After column
ping of two isomers, for the major isomer, s, 3H). 13C NMR chromatography (hexanes/toluene/ethyl acetate 1 : 1 : 1),
(126 MHz, CDCl3, possible peaks are listed) δ 159.8, 158.4, 21.0 mg (36% yield) of a yellow-orange solid was obtained. Rf =
155.1, 142.8, 140.2, 135.5, 132.2, 129.5, 124.4, 122.9, 122.7, 0.27 (hexanes/toluene/ethyl acetate 1 : 1 : 1). 1H NMR
+
121.5, 112.9, 107.1, 55.9. HR-MS (ESI) calcd for C15H11N2O2
[M + H]+: 251.0815, found 251.0831.
(500 MHz, CDCl3) δ 8.24 (d, J = 7.7 Hz, 1H), 8.05 (d, J = 8.8 Hz,
1H), 7.62 (d, J = 3.8 Hz, 2H), 7.48–7.43 (m, 1H), 7.21 (d, J =
8-(Trifluoromethyl)benzofuro[2,3-b]quinoxaline and 9-(tri- 2.3 Hz, 1H), 7.19 (dd, J = 8.9, 2.5 Hz, 1H), 4.25 (bs, 2H).
fluoromethyl)benzofuro[2,3-b]quinoxaline (3da + 3d′a). After 13C NMR (126 MHz, CDCl3) δ 157.6, 156.8, 148.4, 142.3, 136.6,
column chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 136.3, 131.0, 130.4, 124.3, 122.0, 120.2, 112.6, 108.3. HR-MS
56.0 mg (78% yield) of a yellow-white solid (as a 4 : 1 regioiso- (ESI) calcd for
meric product) was obtained. Less than 5% impurity as hydro- 236.0842.
C
14H10N3O+ [M
+
H]+: 236.0818, found
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8,9-Dimethylbenzofuro[2,3-b]quinoxaline (3ha). After 114.1. HR-MS (ESI) calcd for C14H835ClN2O+ [M
column chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 255.0320, found 255.0320.
52.8 mg (85% yield) of a yellow-white solid was obtained. Rf = 2-Bromobenzofuro[2,3-b]quinoxaline (3ad). After column
+
H]+:
1
0.33 (hexanes/ethyl acetate 12 : 1). H NMR (500 MHz, CDCl3) chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 58.9 mg
δ 8.33 (d, J = 7.7 Hz, 1H), 8.05 (s, 1H), 7.90 (s, 1H), 7.71–7.64 (79% yield) of a yellow-white solid was obtained. Rf = 0.32
(m, 2H), 7.51–7.47 (m, 1H), 2.54 (s, 6H). 13C NMR (126 MHz, (hexanes/ethyl acetate 10 : 1). 1H NMR (500 MHz, CDCl3) δ 8.47
CDCl3) δ 158.3, 155.9, 140.7, 140.1, 139.3, 138.8, 138.7, 132.0, (d, J = 2.0 Hz, 1H), 8.29 (dd, J = 8.1, 1.5 Hz, 1H), 8.17 (dd, J =
128.3, 128.0, 124.4, 122.8, 121.6, 112.8, 20.6, 20.4. HR-MS (ESI) 8.2, 1.4 Hz, 1H), 7.85–7.79 (m, 3H), 7.57 (d, J = 8.7 Hz, 1H).
calcd for C16H13N2O+ [M + H]+: 249.1022, found 249.1018.
13C NMR (126 MHz, CDCl3) δ 157.2, 156.0, 141.5, 140.2, 139.3,
8-Bromo-10-methylbenzofuro[2,3-b]quinoxaline and 9-bromo- 135.2, 130.4, 129.5, 128.8, 128.7, 125.8, 123.3, 117.6, 114.5.
7-methylbenzofuro[2,3-b]quinoxaline (3ia + 3i′a). After column HR-MS (ESI) calcd for C14H879BrN2O+ [M + H]+: 298.9815,
chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 26.1 mg found 298.9817.
(33% yield) of a yellow-white solid (as a 7 : 3 regioisomeric
Benzofuro[2,3-b]quinoxaline-2-carbonitrile (3ae). After
product) was obtained. Rf = 0.38 (for both isomers) (hexanes/ column chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1),
ethyl acetate 20 : 1). 1H NMR (500 MHz, CDCl3) δ 8.33–8.29 34.3 mg (56% yield) of a yellow-white solid was obtained. Rf =
(overlapping of two isomers, 1H), 8.28 (minor isomer, dd, 0.35 (hexanes/ethyl acetate 2 : 1). 1H NMR (500 MHz, CDCl3)
J = 2.2, 0.5 Hz, 1H), 8.13 (major isomer, dd, J = 2.2, 0.5 Hz, δ 8.66 (d, J = 1.3 Hz, 1H), 8.35–8.31 (m, 1H), 8.22–8.18 (m, 1H),
1H), 7.75–7.68 (overlapping of two isomers, 2H), 7.68–- 7.99 (dd, J = 8.6, 1.7 Hz, 1H), 7.91–7.85 (m, 2H), 7.81 (d, J =
7.64 (overlapping of two isomers, 1H), 7.54–7.47 (overlapping 8.6 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 160.0, 156.0, 141.9,
of two isomers, 1H), 2.90 (major isomer, s, 3H), 2.82 140.4, 138.6, 135.6, 131.0, 129.7, 129.2, 129.0, 127.5, 122.7,
(minor isomer, s, 0.9H). 13C NMR (126 MHz, CDCl3, possible 118.2, 114.2, 108.9. HR-MS (ESI) calcd for C15H8N3O+ [M + H]+:
peaks are listed)
139.5, 138.8, 133.2, 132.7, 132.4, 131.8, 129.4, 128.9, 124.7,
δ
158.7, 156.1, 140.7, 139.7, 139.6, 246.0662, found 246.0667.
3-Methylbenzofuro[2,3-b]quinoxaline (3af). After column
124.6, 123.6, 123.1, 123.0, 121.6, 121.2, 112.9, 17.8, 17.5. chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 49.3 mg
HR-MS (ESI) calcd for C15H1079BrN2O+ [M + H]+: 312.9971, (84% yield) of a yellow-white solid was obtained. Rf = 0.25
found 312.9981.
(hexanes/ethyl acetate 10 : 1). 1H NMR (500 MHz, CDCl3) δ 8.26
Benzo[g]benzofuro[2,3-b]quinoxaline (3ja). After column (dd, J = 6.5, 3.0 Hz, 1H), 8.18 (d, J = 7.9 Hz, 1H), 8.13 (dd, J =
chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 36.7 mg 6.6, 2.9 Hz, 1H), 7.80–7.73 (m, 2H), 7.46 (s, 1H), 7.29 (d, J =
(54% yield) of a yellow-orange solid was obtained. Rf = 0.33 7.8 Hz, 1H), 2.57 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 159.1,
(hexanes/ethyl acetate 7 : 1). 1H NMR (500 MHz, DMSO-d6) 156.1, 144.1, 141.2, 140.8, 139.6, 129.5, 129.1, 128.7, 128.3,
δ 8.91 (s, 1H), 8.71 (s, 1H), 8.33 (d, J = 7.7 Hz, 1H), 8.28–8.21 125.9, 122.6, 118.7, 113.1, 22.6. HR-MS (ESI) calcd for
(m, 2H), 7.87–7.81 (m, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.67–7.63 C15H11N2O+ [M + H]+: 235.0866, found 235.0897.
(m, 2H), 7.61–7.56 (m, 1H). 13C NMR (126 MHz, DMSO-d6)
3-Methoxybenzofuro[2,3-b]quinoxaline (3ag). After column
δ 158.4, 155.1, 141.9, 137.6, 135.8, 133.2, 132.8, 131.9, 127.8, chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 50.7 mg
127.4, 126.9, 126.5, 125.9, 125.4, 124.4, 122.6, 120.3, 112.3. (81% yield) of a yellow-white solid was obtained. This com-
HR-MS (ESI) calcd for C18H11N2O+ [M + H]+: 271.0856, found pound is known.12 Rf = 0.33 (hexanes/ethyl acetate 2 : 1).
271.0851.
1H NMR (500 MHz, DMSO-d6) δ 8.24–8.20 (m, 1H), 8.18 (d, J =
2-Fluorobenzofuro[2,3-b]quinoxaline (3ab). After column 8.6 Hz, 1H), 8.10–8.06 (m, 1H), 7.84–7.80 (m, 2H), 7.42 (d, J =
chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 47.9 mg 2.2 Hz, 1H), 7.14 (dd, J = 8.6, 2.2 Hz, 1H), 3.97 (s, 3H).
(81% yield) of a yellow-white solid was obtained. This com- 13C NMR (126 MHz, DMSO-d6) δ 163.5, 159.6, 155.3, 140.4,
pound is known.3c Rf = 0.35 (hexanes/ethyl acetate 15 : 1). 140.0, 137.9, 128.7, 128.2, 127.77, 127.72, 123.1, 112.9, 112.7,
1H NMR (500 MHz, CDCl3) δ 8.30 (d, J = 7.8 Hz, 1H), 8.17 (d, 97.5, 55.9.
J = 7.8 Hz, 1H), 8.01 (dd, J = 7.1, 2.0 Hz, 1H), 7.86–7.78 (m,
3-Bromo-2-methylbenzofuro[2,3-b]quinoxaline (3ah). After
2H), 7.64 (dd, J = 9.0, 3.8 Hz, 1H), 7.43 (td, J = 8.9, 2.6 Hz, 1H). column chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1),
13C NMR (126 MHz, CDCl3) δ 159.6 (d, J = 244.3 Hz), 156.5, 19.1 mg (24% yield) of a yellow-white solid was obtained. Rf =
154.3, 141.2, 140.0, 130.2, 129.3, 128.7, 128.5, 122.3 (d, J = 0.33 (hexanes/ethyl acetate 8 : 1). 1H NMR (500 MHz, CDCl3)
9.6 Hz), 119.7 (d, J = 25.9 Hz), 113.8 (d, J = 8.6 Hz), 109.0 (d, J = δ 8.28–8.24 (m, 1H), 8.17 (s, 1H), 8.16–8.12 (m, 1H), 7.89 (s,
25.4 Hz). One carbon signal could not be located.
1H), 7.83–7.76 (m, 2H), 2.58 (s, 3H). 13C NMR (126 MHz,
2-Chlorobenzofuro[2,3-b]quinoxaline (3ac). After column CDCl3) δ 156.8, 156.1, 141.5, 140.0, 139.9, 134.6, 130.0, 129.3,
chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 52.3 mg 128.8, 128.6, 123.7, 120.7, 116.8, 23.2. HR-MS (ESI) calcd for
(82% yield) of a yellow-white solid was obtained. Rf = 0.38 C15H1079BrN2O+ [M + H]+: 312.9952, found 312.9971.
(hexanes/ethyl acetate 10 : 1). 1H NMR (500 MHz, CDCl3) δ 8.33
Naphtho[2′,1′:4,5]furo[2,3-b]quinoxaline (3ai). After column
(d, J = 2.0 Hz, 1H), 8.32–8.29 (m, 1H), 8.20–8.17 (m, 1H), chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 34.4 mg
7.87–7.80 (m, 2H), 7.68 (dd, J = 8.7, 2.0 Hz, 1H), 7.63 (d, J = (51% yield) of a yellow solid was obtained. Rf = 0.31 (hexanes/
1
8.7 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 156.8, 156.2, 141.6, ethyl acetate 6 : 1). H NMR (500 MHz, DMSO-d6) δ 8.49 (d, J =
140.2, 139.6, 132.4, 130.4, 129.5, 128.9, 128.7, 122.83, 122.78, 7.9 Hz, 1H), 8.35–8.31 (m, 1H), 8.29 (d, J = 8.5 Hz, 1H), 8.21
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(d, J = 7.6 Hz, 1H), 8.20–8.16 (m, 1H), 8.07 (d, J = 8.5 Hz, 1H), 150.1, 142.0, 140.9, 140.3, 135.7, 134.4, 132.4, 132.2, 131.2,
7.93–7.88 (m, 2H), 7.86–7.79 (m, 2H). 13C NMR (126 MHz, 130.8, 130.3, 130.1, 129.7, 126.44, 126.36, 125.3, 123.9, 118.3,
DMSO-d6) δ 155.2, 154.8, 140.8, 140.1, 138.5, 134.9, 129.2, 113.0. HR-MS (ESI) calcd for C15H7N3NaS+ [M + Na]+: 284.0253,
128.52, 128.49, 128.47, 128.1, 128.0, 127.4, 124.8, 120.5, 119.9, found 284.0259.
117.8, 115.7. HR-MS (ESI) calcd for C18H11N2O+ [M + H]+:
271.0856, found 271.0866.
8,9-Dimethylbenzo[4,5]thieno[2,3-b]quinoxaline (5ha). After
column chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1),
2,4-Dibromobenzofuro[2,3-b]quinoxaline (3aj). After column 52.4 mg (79% yield) of a yellow-white solid was obtained. Rf =
chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 32.5 mg 0.34 (hexanes/ethyl acetate 7 : 1). 1H NMR (500 MHz, CDCl3)
(34% yield) of a yellow-white solid was obtained. Rf = 0.37 δ 8.53 (d, J = 7.7 Hz, 1H), 7.99 (s, 1H), 7.87 (s, 1H), 7.84 (d, J =
(hexanes/ethyl acetate 15 : 1). 1H NMR (500 MHz, CDCl3) δ 8.40 7.9 Hz, 1H), 7.62 (t, J = 7.5 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 2.52
(d, J = 1.9 Hz, 1H), 8.31–8.27 (m, 1H), 8.20–8.16 (m, 1H), 7.99 (s, 6H). 13C NMR (126 MHz, CDCl3) δ 140.7, 139.8, 139.7,
(d, J = 1.9 Hz, 1H), 7.89–7.80 (m, 2H). 13C NMR (126 MHz, 131.9, 130.6, 128.6, 127.5, 125.7, 124.2, 123.6, 20.6, 20.5.
CDCl3) δ 155.7, 154.7, 141.8, 140.4, 139.1, 137.3, 130.9, 129.6, HR-MS (ESI) calcd for C16H13N2S+ [M + H]+: 265.0794, found
129.1, 129.0, 124.6, 124.5, 117.8, 106.7. HR-MS (ESI) calcd for 265.0791.
C14H779Br2N2O+ [M + H]+: 376.8920, found 376.8910.
9-Chlorobenzo[4,5]thieno[2,3-b]quinoxaline and 8-chloro-
Benzo[4,5]thieno[2,3-b]quinoxaline (5aa). After column benzo[4,5]thieno[2,3-b]quinoxaline (5la + 5l′a). After column
chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 51.0 mg chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 42.8 mg
(86% yield) of a yellow-white solid was obtained. This com- (63% yield) of a white-yellow solid (as an 8 : 1 regioisomeric
pound is known.3a When 2′-bromoacetophenone (0.25 mmol, product) was obtained. This compound is known.3a Rf = 0.36
49.8 mg) was used, 46.0 mg (78% yield) of the desired product (major) and 0.30 (minor) (hexanes/ethyl acetate 12 : 1).
was obtained. When 2′-nitroacetophenone (0.25 mmol, 1H NMR (500 MHz, CDCl3) δ 8.56–8.54 (overlapping of two
41.3 mg) was used, 19.0 mg (32% yield) of the desired product isomers, 1H), 8.26 (major isomer, d, J = 2.2 Hz, 1H), 8.20
1
was obtained. Rf = 0.35 (hexanes/ethyl acetate 10 : 1). H NMR (minor isomer, d, J = 9.0 Hz, 1H), 8.14 (minor isomer, d, J =
(500 MHz, CDCl3) δ 8.54 (dd, J = 7.8, 0.6 Hz, 1H), 8.27–8.23 (m, 2.2 Hz, 1H), 8.08 (major isomer, d, J = 9.0 Hz, 1H), 7.88–7.86
1H), 8.15–8.11 (m, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.81–7.75 (m, (overlapping of two isomers, 1H), 7.75–7.73 (overlapping of
2H), 7.65–7.60 (m, 1H), 7.57–7.52 (m, 1H). 13C NMR (126 MHz, two isomers, 1H), 7.70–7.66 (overlapping of two isomers, 1H),
CDCl3) δ 157.4, 147.9, 141.5, 140.5, 140.1, 131.5, 131.0, 129.8, 7.60–7.57 (overlapping of two isomers, 1H). 13C NMR
129.6, 129.1, 128.4, 125.8, 124.5, 123.6.
(126 MHz, CDCl3, possible peaks are listed) δ 157.6, 148.6,
9-Methylbenzo[4,5]thieno[2,3-b]quinoxaline and 8-methyl- 140.9, 140.4, 140.0, 134.9, 131.5, 131.2, 130.8, 129.6, 128.5,
benzo[4,5]thieno[2,3-b]quinoxaline (5ba + 5b′a). After column 126.0, 124.8, 123.7.
chromatography (hexanes/ethyl acetate 100 : 1 to 5 : 1), 52.6 mg
2-(Trifluoromethyl)benzo[4,5]thieno[2,3-b]quinoxaline (5ab).
(84% yield) of a yellow-white solid (as an 8 : 1 regioisomeric After column chromatography (hexanes/ethyl acetate 100 : 1 to
product) was obtained. The major isomer is known.3a Rf = 0.30 5 : 1), 26.1 mg (34% yield) of a pink solid was obtained. Rf =
1
(for both isomers) (hexanes/ethyl acetate 8 : 1). 1H NMR 0.32 (hexanes/ethyl acetate 12 : 1). H NMR (500 MHz, CDCl3)
(500 MHz, CDCl3) δ 8.59 (major isomer, d, J = 7.8 Hz, 1H), 8.56 δ 8.87–8.84 (m, 1H), 8.33–8.28 (m, 1H), 8.21–8.16 (m, 1H), 8.00
(minor isomer, d, J = 7.8 Hz, 1H), 8.17 (minor isomer, d, J = (d, J = 8.3 Hz, 1H), 7.90 (dd, J = 8.3, 1.3 Hz, 1H), 7.89–7.83 (m,
8.6 Hz, 0.11H), 8.06–8.03 (major isomer, m, 2H), 7.92 (minor 2H). 13C NMR (126 MHz, CDCl3, possible peaks are listed)
isomer, s, 1H), 7.87–7.75 (overlapping of two isomers, 1H), δ 157.1, 146.8, 143.7, 143.7, 141.9, 140.8, 131.9, 130.6, 129.8,
7.68–7.62 (overlapping of two isomers, 2H), 7.59–7.56 (overlap- 129.7, 128.6, 127.2 (q, J = 3.5 Hz), 124.2, 121.5 (q, J = 4.1 Hz).
ping of two isomers, 1H), 2.64 (overlapping of two isomers, HR-MS (ESI) calcd for C15H8F3N2S+ [M + H]+: 305.0355, found
3H). 13C NMR (126 MHz, CDCl3, possible peaks are listed) 305.0353.
δ 156.5, 147.6, 141.6, 140.7, 140.5, 140.15, 140.11, 139.8, 132.3,
131.66, 131.59, 131.0, 130.8, 129.1, 128.3, 128.0, 127.3, 125.8, After column chromatography (hexanes/ethyl acetate 100 : 1 to
124.5, 124.3, 123.7, 22.1, 22.0. 5 : 1), 47.4 mg (52% yield) of a yellow-white solid was obtained.
3-(4-Chlorophenoxy)benzo[4,5]thieno[2,3-b]quinoxaline (5ac).
Benzo[4,5]thieno[2,3-b]quinoxaline-8-carbonitrile and benzo Rf = 0.32 (hexanes/ethyl acetate 7 : 1). 1H NMR (500 MHz,
[4,5]thieno[2,3-b]quinoxaline-9-carbonitrile (5ea + 5e′a). After CDCl3) δ 8.50 (d, J = 8.6 Hz, 1H), 8.26–8.22 (m, 1H), 8.15–8.11
column chromatography (toluene/ethyl acetate 100 : 1 to (m, 1H), 7.82–7.76 (m, 2H), 7.41–7.37 (m, 2H), 7.37 (d, J = 2.3
20 : 1), 42.9 mg (66% yield) of a yellow solid (as a 5 : 1 regioiso- Hz, 1H), 7.20 (dd, J = 8.6, 2.2 Hz, 1H), 7.10–7.06 (m, 2H).
meric product) was obtained. Rf = 0.33 (for both isomers) 13C NMR (126 MHz, CDCl3) δ 160.2, 157.3, 154.6, 147.4, 142.0,
1
(toluene/ethyl acetate 40 : 1). H NMR (500 MHz, CDCl3) δ 8.64 141.0, 140.6, 130.3, 130.0, 129.6, 129.5, 129.3, 128.5, 126.7,
(minor isomer, d, J = 1.7 Hz, 1H), 8.59–8.57 (overlapping of 125.9, 121.5, 116.9, 112.2. HR-MS (ESI) calcd for
two isomers, 1H), 8.51 (major isomer, d, J = 1.7 Hz, 1H), 8.34 C20H1235ClN2OS+ [M + H]+: 363.0353, found 363.0348.
(major isomer, d, J = 8.7 Hz, 1H), 8.22 (minor isomer, d, J =
2-Chlorothieno[3′,2′:4,5]thieno[2,3-b]quinoxaline (5ad). After
8.7 Hz, 1H), 7.93–7.89 (overlapping of two isomers, 2H), column chromatography (hexanes/ethyl acetate 100 : 1 to
7.75–7.72 (overlapping of two isomers, 1H), 7.64–7.61 (overlap- 10 : 1), 7.2 mg (10% yield) of a yellow solid was obtained. Rf =
1
ping of two isomers, 1H). 13C NMR (126 MHz, CDCl3) δ 159.4, 0.36 (hexanes/ethyl acetate 12 : 1). H NMR (500 MHz, CDCl3)
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δ 8.23–8.20 (m, 1H), 8.15–8.12 (m, 1H), 7.85–7.77 (m, 2H), 7.72
(s, 1H). 13C NMR (126 MHz, CDCl3) δ 159.2, 144.1, 141.1,
140.5, 139.8, 135.3, 132.1, 129.8, 129.6, 129.4, 128.7, 120.3.
Notes and references
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G. Zanardi, J. Org. Chem., 1997, 62, 8394; (b) B. Hu,
P. Zhou, Q. Zhang, Y. Wang, S. Zhao, L. Lu, S. Yan and
F. Yu, J. Org. Chem., 2018, 83, 14978; (c) J. Liu,
A. E. Fitzgerald and N. S. Mani, J. Org. Chem., 2008, 73,
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G.-U. Flechsig and P. Langer, Org. Biomol. Chem., 2014, 12,
6151.
4 (a) T. B. Nguyen and P. Retailleau, Adv. Synth. Catal., 2017,
359, 3843; (b) T. B. Nguyen, L. A. Nguyen and P. Retailleau,
Org. Lett., 2019, 21, 6570; (c) S. Deng, H. Chen, X. Ma,
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387; (b) P. H. Pham, K. X. Nguyen, H. T. B. Pham,
T. T. Nguyen and N. T. S. Phan, Org. Lett., 2019, 21, 8795;
(c) X. Chen, Z. Wang, H. Huang and G.-J. Deng, Adv. Synth.
Catal., 2018, 360, 4017.
6 (a) T. B. Nguyen and P. Retailleau, Adv. Synth. Catal., 2017,
359, 3843; (b) T. B. Nguyen, L. A. Nguyen and P. Retailleau,
Org. Lett., 2019, 21, 6570; (c) Y. Liao, Y. Peng, H. Qi,
G.-J. Deng, H. Gong and C.-J. Li, Chem. Commun., 2015, 51,
1031; (d) X. Chen, Z. Wang, H. Huang and G.-J. Deng, Adv.
Synth. Catal., 2018, 360, 4017.
7 For selected examples, see: (a) Y. Wei and N. Yoshikai,
J. Am. Chem. Soc., 2013, 135, 3756; (b) B. Zhao, H.-W. Liang,
J. Yang, Z. Yang and Y. Wei, ACS Catal., 2017, 7, 5612.
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and N. T. S. Phan, Org. Biomol. Chem., 2019, 17, 8987;
(b) T. H. Ho, H. H. K. Le, T. A. To, T. T. Nguyen and
N. T. S. Phan, Bull. Chem. Soc. Jpn., 2020, 93, 783.
9 See the ESI† for more details.
+
HR-MS (ESI) calcd for C12H6ClN2S2 [M + H]+: 276.9655, found
276.9705.
6-Benzyl-6H-indolo[2,3-b]quinoxaline (7aa). After column
chromatography (toluene/ethyl acetate 100 : 1 to 50 : 1),
60.1 mg (78% yield) of a yellow solid was obtained. This com-
pound is known.3d Rf = 0.35 (toluene/ethyl acetate 100 : 1).
1H NMR (500 MHz, CDCl3) δ 8.49 (d, J = 7.6 Hz, 1H), 8.33 (dd,
J = 8.3, 1.2 Hz, 1H), 8.15 (dd, J = 8.4, 1.2 Hz, 1H), 7.76 (ddd, J =
8.3, 6.9, 1.5 Hz, 1H), 7.69 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H),
7.63–7.57 (m, 1H), 7.39–7.31 (m, 4H), 7.31–7.23 (m, 3H), 5.72
(s, 2H). 13C NMR (126 MHz, CDCl3) δ 146.0, 144.5, 140.8,
140.2, 139.7, 136.7, 131.2, 129.5, 128.97, 128.94, 128.0, 127.8,
127.4, 126.3, 122.9, 121.3, 119.8, 110.3, 45.2.
8,9-Dimethoxy-6H-indolo[2,3-b]quinoxaline (7ab). After
column chromatography (gradient 0% to 5% methanol in
ethyl acetate), 46.5 mg (67% yield) of a yellow-orange solid was
obtained. Rf = 0.29 (hexanes/ethyl acetate 1 : 1). 1H NMR
(500 MHz, DMSO-d6) δ 11.76 (s, 1H), 8.17 (dd, J = 8.2, 1.3 Hz,
1H), 8.02 (dd, J = 8.3, 1.2 Hz, 1H), 7.79 (s, 1H), 7.73 (ddd, J =
8.3, 6.9, 1.5 Hz, 1H), 7.67 (ddd, J = 8.2, 6.9, 1.5 Hz, 1H), 7.10 (s,
1H), 3.95 (s, 3H), 3.91 (s, 3H). 13C NMR (126 MHz, DMSO-d6)
δ 153.4, 145.9, 144.9, 140.0, 139.8, 139.1, 138.5, 128.6, 127.7,
127.4, 125.7, 110.0, 104.1, 95.4, 56.1, 55.9. HR-MS (ESI) calcd
for C16H14N3O2+ [M + H]+: 280.1081, found 280.1094.
5H-Pyrazino[2,3-b]indole (8). After column chromatography
(chloroform/ethyl acetate 100 : 1 to 1 : 1), 8.4 mg (20% yield) of
a brown solid was obtained. This compound is known.13 Rf =
0.38 (hexanes/ethyl acetate 3 : 1). 1H NMR (500 MHz, DMSO-d6)
δ 12.12 (s, 1H), 8.49 (d, J = 2.7 Hz, 1H), 8.44 (d, J = 2.7 Hz, 1H),
8.23 (d, J = 7.8 Hz, 1H), 7.64–7.57 (m, 2H), 7.36–7.31 (m, 1H).
13C NMR (126 MHz, DMSO-d6) δ 145.5, 140.2, 139.9, 136.4,
135.2, 129.0, 120.9, 120.5, 119.3, 112.1.
Benzo[4,5]thieno[2,3-b]pyrazine (9). After column chromato-
graphy (hexanes/ethyl acetate 100 : 1 to 5 : 1), 7.5 mg (16%
yield) of an ivory yellow solid was obtained. Rf = 0.37 (hexanes/
1
ethyl acetate 5 : 1). H NMR (500 MHz, CDCl3) δ 8.68 (d, J = 2.5
Hz, 1H), 8.56 (d, J = 2.5 Hz, 1H), 8.47 (ddd, J = 7.7, 1.4, 0.7 Hz,
1H), 7.92–7.88 (m, 1H), 7.63 (td, J = 7.6, 1.4 Hz, 1H), 7.58 (td,
J = 7.6, 1.1 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 157.2, 147.0,
142.0, 141.0, 139.0, 132.0, 129.8, 125.7, 123.7, 123.4. HR-MS
(ESI) calcd for C10H7N2S+ [M + H]+: 187.0324, found 187.0357.
10 (a) T. T. H. Le, C. Youhei, Q. H. Le, T. B. Nguyen and
D. H. Mac, Org. Biomol. Chem., 2019, 17, 6355; (b) Z. Xu,
G.-J. Deng, F. Zhang, H. Chen and H. Huang, Org. Lett.,
2019, 21, 8630.
Conflicts of interest
There are no conflicts to declare.
11 S. C. Sahoo, U. Nath and S. C. Pan, Eur. J. Org. Chem., 2017,
4434.
12 K. S. Kumar, R. Adepu, R. Kapavarapu, D. Rambabu,
G. R. Krishna, C. M. Reddy, K. K. Priya, K. V. L. Parsa and
M. Pal, Tetrahedron Lett., 2012, 53, 1134.
Acknowledgements
The Viet Nam National Foundation for Science and
Technology Development (NAFOSTED) is acknowledged for
supporting this research under Project code 104.01-2019.340 13 P. Z. Mannes, E. O. Onyango and G. W. Gribble, J. Org.
(for Nam T. S. Phan).
Chem., 2016, 81, 12478.
Org. Biomol. Chem.
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