Acid-Catalyzed Condensation of o-Phenylenediammines and o-Aminophenols with α-Oxodithioesters: A Divergent and Regio? selective Synthesis of 2-Methylthio-3-Aryl/Heteroarylquinoxalines and 2-Acylbenzoxazoles

Article abstract of DOI:10.1055/s-0039-1690616

o-Phenylenediammines and o-Aminophenols were reacted with α-oxodithioesters in a highly regioselective fashion to give 2-methylthio-3-Aryl/heteroarylquinoxalines and 2-Acylbenzoxazoles in 55-94percent and 45-86percent, respectively, in the presence of p-T

Full text of DOI:10.1055/s-0039-1690616

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–J
paper
A
en
K. R. Kiran et al.
Paper
Synthesis
Acid-Catalyzed Condensation of o-Phenylenediammines and
o-Aminophenols with -Oxodithioesters: A Divergent and Regio-
selective Synthesis of 2-Methylthio-3-aryl/Heteroarylquinoxalines
and 2-Acylbenzoxazoles
Kuppalli R Kirana
Toreshettahally R Swaroop*b
Kodipura P Sukruthaa
Jeegundipattana B Shruthia
Seegehally M Anila
Kanchugarakoppal S Rangappa*a
Maralinganadoddi P Sadashiva*a
NH2
OH
0
0
0
0-0
0
0
2-0
0
8
7-
6
3
3
1
R'
R''
O
R
N
S
R
O
N
S
SMe
R
NH2
NH2
R''
R'
p-TSA/Toluene
80 °C, 1 h
p-TSA/Toluene
80 °C, 2 h
N
O
12 examples
45–86% yield
12 examples
R = Aryl/hetaryl
R = Aryl/hetaryl
55–94% yield
R'= H, Br, CF3 and NO2
R''= H, Me and NO2
0
0
0
0-0
0
0
2-
1
5
2
8-9
4
4
7
a Department of Studies in Chemistry, University of Mysore,
Manasagangothri, Mysuru, 570 006, India
rangappaks@gmail.com
mpsadashiva@gmail.com
b Department of Studies in Organic Chemistry, University of
Mysore, Manasagangothri, Mysuru, 570 006, India
swarooptr@gmail.com
Received: 26.06.2019
Accepted after revision: 06.08.2019
Published online: 23.09.2019
of 2-iodoanilines, aryl acetaldehydes and sodium azide13
and N-aryl ketimines with sodium azide,14 reductive cou-
pling of 2-nitroanilines with 1,2-diketones,15 heteroannula-
tion of nitro ketene N,S-arylaminoacetals with POCl3,16 nuc-
leophilic substitution on o-nitrohalobenzene by aliphatic
amine followed by reductive cyclization17 and cyclization of
-aryliminophenylhydrazone18 or oxime derivatives19 of -
dicarbonyl compounds with anilines.
On the other hand, the benzoxazole skeleton can be
constructed by the reaction of o-aminophenol with alde-
hydes,20 aryl and vinyl bromides,21 -diketones,22 orthoe-
sters,23 carboxylic acids,24 ketones,25 and isocyanides.26 Oth-
er strategies include intramolecular cyclization of o-bro-
moaryl amides,27 cyclization of o-hydroxyaryl N-H
ketimines,28 copper-catalyzed conversion of bisaryloxime
ethers,29 and oxidative cyclization of o-hydroxy-N-aryl-N,N-
dialkylformamidines.30
DOI: 10.1055/s-0039-1690616; Art ID: ss-2019-m0356-op
Abstract o-Phenylenediammines and o-aminophenols were reacted
with -oxodithioesters in a highly regioselective fashion to give 2-meth-
ylthio-3-aryl/heteroarylquinoxalines and 2-acylbenzoxazoles in 55–94%
and 45–86%, respectively, in the presence of p-toluene sulfonic acid
catalyst. Control experiments involving reaction of aniline with a -oxo-
dithioester indicated that the thiocarbonyl group is more reactive than
the carbonyl group. Based on this, probable mechanisms for the forma-
tion of quinoxalines and benzoxazoles are given. Biological targets of
the quinoxalines and benzoxazoles were identified by bioinformatics. It
was found that quinoxalines have good binding affinity with human
dual-specificity tyrosine-phosphorylation-regulated kinase 1A and ben-
zoxazoles with human carboxylesterase.
Key words -oxodithioester, quinoxaline, benzoxazole, condensation,
p-TSA
In particular, reaction of o-phenylenediammines with
pyruvates (Hinsberg and Körner synthesis)31 gives 3-substi-
tuted quinoxalin-2(1H)-ones.32 Our literature survey re-
vealed that reaction of o-phenylenediammines with sulfur
analogues of pyruvates (2-oxo-2-(het)arylethanedithioates)
to give 2-methylthio-3-aryl/heteroarylquinoxalines, has
not been reported. Other synthetic methods to access 2-ac-
ylbenzoxazoles are very limited. The available methods in-
clude transition-metal-catalyzed cyclization of 1,1-dibro-
moethenes33 and alkynyl bromides34 with 2-aminophenols,
and oxidative cyclization of N-(2-hydroxyphenyl)-4-meth-
yl-N-(phenacyl)benzene sulfonamides.35 Preconstructed
benzoxazole can also be functionalized to get 2-acylben-
zoxazoles.36 In general, many of these methods suffer from
Quinoxalines and benzoxazoles are important members
of the family of azaheterocycles. They display a broad range
of biological activities,1 which makes them privileged scaf-
folds in drug discovery.2 They are present in many dyes and
organic semiconductors.3 As a consequence, increasing
numbers of new methods are being reported for their syn-
thesis. In particular, the challenging synthesis of functional-
ized azaheterocycles is a subject of great importance.
Quinoxalines can be synthesized by the reaction of o-
phenylenediammine with 1,2-diketones,4 -hydroxyke-
tones,5 epoxides,6 -bromoketones,7,4h terminal alkynes,8
aldehydes,9 deoxybenzoins,10 -aryl amines,11 and ynones.12
Other approaches include, copper-catalyzed condensation
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–J
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
K. R. Kiran et al.
Paper
Synthesis
drawbacks such as the use of toxic/volatile organic solvents,
transition-metal catalysts, long reaction times, poor yields,
harsh reaction conditions and tedious work-up procedures.
To our knowledge, the synthesis of 2-acylbenzoxazoles
from activated dithioates has not been reported.
of p-TSA at 80 °C (Scheme 1, and Table S1, entry 6). Replace-
ment of toluene with ethanol did not improve the yield (Ta-
ble S1, entry 8). The reaction was successful even in the
presence of base catalysts such as DBU and triethylamine,
but yields were reduced (Table S1, entries 9 and 10). Sur-
prisingly, the other possible product (1H-benzo[d]imidazol-
2-yl)(phenyl)methanone (3aa; Scheme 1) was not ob-
served. Thus, the product 3a was formed in highly regio-
selective fashion.
With the optimized reaction conditions, the generality
of the protocol was tested by conducting reactions with
various -oxodithioesters bearing halogens such as F, Cl,
and Br at various positions, which yielded the respective 2-
(methylthio)-3-arylquinoxalines 3b–d in 92–94% yield
(Scheme 1). -Oxodithioesters with electron-withdrawing
or electron-donating groups also furnished 2-(methylthio)-
3-(aryl)quinoxalines 3e–g in 87–93% yield. The 2-(meth-
ylthio)-3-(naphthalen-1-yl) quinoxaline (3h) was obtained
in 84% yield from methyl-2-(naphthalen-1-yl)-2-oxoethan-
edithioate. The methyl 2-oxo-2-(thiophen-2-yl)ethanedith-
ioate also afforded 2-(methylthio)-3-(thiophen-2-yl)qui-
noxaline (3i) in 90% yield upon condensation with 1. Final-
ly, 4-bromobenzene-1,2-diamine (with electron-donating
bromo group) also gave the corresponding 6-bromo-2-
(methylthio)-3-phenylquinoxaline (3j) in 92% yield. Simi-
larly, 4-trifluromethyl/nitrobenzene-1,2-diamine furnished
the respective 6-trifluoromethyl/nitro-2-(methylthio)-3-
phenylquinoxaline 3k and 3l in 55% and 58% yield, which
were less than for the unsubstituted and bromo-1,2-diam-
-Oxodithioesters have been known from a long time37
but their synthetic applications have not been extensively
explored to date. In a few reports, they were used as dieno-
philes in thia-Diels–Alder reaction.38 Furthermore, they re-
acted with diazomethane to give 1,3-oxathiole, which can
react with maleic anhydride to give tetrahydrothiene.39 The
synthesis of both quinoxaline and benzoxazole from the
same substrate with subtle variation in regioselectivity is
not known. As a part of our work on the development of
new synthetic methods40 for biologically interesting hetero-
cyclic compounds, we have designed new organosulfur
building blocks and explored their applications.41 In a con-
tinuation of these studies, we now disclose a highly regio-
selective cyclization of o-phenylenediammines and o-amino-
phenols with -oxodithioesters to get quinoxalines and
benzoxazoles, respectively.
We started our study with the cyclocondensation of o-
phenylenediammine 1 with methyl 2-oxo-2-phenylethan-
edithioate 2a in the presence of various acid catalysts such
as p-toluenesulfonic acid (p-TSA), trifluoroacetic acid, acetic
acid and methanesulfonic acid in toluene as a solvent at
various temperatures (Table S1, entries 1–7; Supporting In-
formation). The highest yield of 2-(methylthio)-3-
phenylquinoxaline (3a; 90%) was obtained in the presence
NH2
N
N
S
R
S
SMe
R
p-TSA
p-TSA
N
R'
R'
R'
toluene, 80 °C, 1 h
toluene, 80 °C, 1 h
NH2
O
N
H
O
1
2
3
3aa
N
S
N
N
S
N
S
N
S
Br
N
N
N
3d (94%)
F
S
Cl
3c (93%)
3b (92%)
3a (90%)
N
N
S
N
S
N
N
S
N
N
N
NO2
3e (89%)
O
3f (93%)
3h (84%)
3g (87%)
N
N
S
O2N
N
S
F3C
N
N
S
N
S
S
N
Br
N
3l (58%)
3i (90%)
3k (55%)
3j (92%)
Scheme 1 Synthesis of 2-aryl-3-methylthioquinoxalines 3. Reagents and conditions: 1 (1 mmol), 2 (1 mmol), p-TSA (0.1 mmol), toluene (3 mL), 80 °C,
1 h.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–J

C
K. R. Kiran et al.
Paper
Synthesis
mine. In none of the examples the other possible isomer 3-
acylbenzimidazole was observed, which indicates the high
regioselectivity in the formation of 2-methylthio-3-aryl/he-
teroarylquinoxalines.
oxodithioesters underwent condensation with o-amino-
phenol and substituted o-aminophenol (electron-donating
methyl and electron-withdrawing nitro substituents) to
give the respective benzoxazoles 5i–l in 45–82% yield. The
structure of benzoxazole 5i was confirmed by X-ray diffrac-
tion studies, and its ORTEP diagram is given in Figure 1.
These reactions reflect the change in regioselective cycliza-
tion on changing the bi-nucleophile from o-phenylene-
diammine to o-aminophenol.
Later, we conducted cyclocondensation of o-aminophe-
nol (4) with methyl 2-oxo-2-phenylethanedithioate (2a) in
the presence of different acid catalysts such as p-TSA, triflu-
oroacetic acid, acetic acid and methane sulfonic acid in tol-
uene as a solvent of choice at varying temperatures (Table
S2, entries 1–8, Supporting Information). The highest yield
of benzo[d]oxazol-2-yl(phenyl)methanone (5a) (75%;
Scheme 2) was obtained in the presence of p-TSA at 80 °C
(Table S2, entry 6). The desired product 5a was obtained
even in the presence of bases like triethylamine and DBU
(Table S2, entry 9–10). Conducting the reaction in ethanol
did not give the desired product (Table S2, entry 11).
The generality of cyclocondensation of o-aminophenol
with -oxodithioesters under the optimized reaction condi-
tions to afford 2-acylbenzoxazoles was explored (Scheme
2). 2-Oxo-2-phenylethanedithioate furnished benzo[d]ox-
azol-2-yl(phenyl)methanone (5a) in 75% yield. Later, the
versatility of the reaction was investigated with various -
oxodithioesters bearing halogens, which afforded the corre-
sponding benzoxazoles 5b–d in 78–84% yield. Furthermore,
benzo[d]oxazol-2-yl(aryl)methanones 5e–g were obtained
in 75–86% yield. Various aryl and heteroaryl substituted -
Figure 1 ORTEP diagram of (5-methylbenzo[d]oxazol-2-yl)(phenyl)
methanone (5i)
The required starting materials -oxodithioesters 2
were synthesized according to the earlier reported protocol
(Scheme 3).37 Reaction of methyl ketones 6 with iodine in
pyridine solvent gave pyridinium iodide 7 in quantitative
yield. Further treatment with sulfur in the presence of
trimethylamine followed by reaction with methyl iodide af-
forded -oxodithioesters 2 in moderate to good yields (52–
65%). In this way, various substrates 2a–j were synthesized
bearing phenyl, substituted phenyl (halogens, electron-do-
nating groups and electron-withdrawing groups), naphthyl
and thienyl groups. However, attempts to synthesize -oxo-
dithioesters with aliphatic substituents were unsuccessful.
The characterization data are given in the Supporting Infor-
mation.
OH
O
R
S
O
R
O
N
p-TSA
R''
R''
toluene, 80 °C, 2 h
MeS
NH2
2
5
4
O
O
N
O
O
O
O
N
N
5c (80%)
5b (78%)
5a (75%)
Cl
F
O
O
N
O
O
O
O
N
N
5f (75%)
5e (86%)
5d (84%)
NO2
Br
O
O
R
S
O
1. S8, Et3N
2. MeI
I2, pyridine
O
O
N
O
O
O
N
O
N
N
R
R
SMe
I
6
S
7
2
Scheme 3 Synthesis of -oxodithioesters 2
5i (82%)
5h (82%)
5g (77%)
O
O
O
O
O
O
O
To establish whether nucleophilic attack of the amine
took place on the thiocarbonyl or carbonyl group, we con-
ducted a control experiment involving the reaction of ani-
line 8 with methyl 2-oxo-2-phenylethanedithioate (2a), un-
der the optimized reaction conditions. The reaction result-
ed in the formation of 2-oxo-N,2-diphenylethanethioamide
(9) through the elimination of methane thiol, which indi-
N
O2N
N
N
S
5l (45%)
5k (80%)
5j (79%)
O
Scheme 2 Synthesis of 2-acylbenzoxazoles 5. Reagents and conditions:
4 (1 mmol), 2 (1 mmol), p-TSA (0.1 mmol), toluene (3 mL), 80 °C, 2 h.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–J

D
K. R. Kiran et al.
Paper
Synthesis
cates that the thiocarbonyl group is more reactive than the
carbonyl group (Scheme 4a). When 1 was reacted with 2a
in the absence of catalyst p-TSA in toluene at 80 °C, the de-
sired product 3a was furnished in only 10% yield (Scheme
4b). Thus, this experiment indicates the requirement of cat-
alyst p-TSA for the cyclocondensation.
furnishes quinoxalines 3. On the other hand, acid-catalyzed
condensation of o-aminophenol 4 with protonated -oxo-
dithioester 10 gives intermediate 15 (Scheme 6). Elimina-
tion of methane thiol from 15 furnished -ketothioamide
17 via the thio-enol tautomer 16. Further acid-catalyzed
cyclocondensation of 18 gave benzoxazole 5 via intermedi-
ate 19 through the elimination of H2S (Scheme 6). However,
in reactions with o-phenylenediammine and o-aminophe-
nol, intermediates 12, 16, and 17 were not detected, proba-
bly because they were short lived in the reaction. Neverthe-
less, we tried to identify the intermediates by controlling
the temperature of the reaction, which directly furnished
the final products in varying yields; however these inter-
mediates were also unidentifiable (Table S1 and S2, Sup-
porting Information).
(a)
H
S
S
N
S
NH2
p-TSA
+
+
toluene, 80 °C, 1 h
O
Ph
O
Ph
8
2a
9 (65%)
(b)
S
N
S
S
NH2
NH2
toluene, 80 °C, 1 h
N
Ph
O
Ph
1
2a
3a (10%)
The target prediction of quinoxalines and benzoxazoles
was conducted based on well-established bioinformatics
techniques.42 The studies showed that quinoxalines have
good binding affinity with human dual-specificity tyrosine-
phosphorylation-regulated kinase 1A (PDB ID: 2WO6) and
benzoxazoles with human carboxylesterase (PDB ID: 2H7C).
Quinoxalines and benzoxazoles exhibited good docking
scores in the range –6.706 to –5.414 and –6.316 to –4.92 re-
spectively. The binding of quinoxalines 3h and 3a, and ben-
zoxazoles 5c and 5e, with respective targets are given in
Figure 2. The docking scores of all compounds are given in
the Supporting Information.
Scheme 4 Control experiments
Based on the results of the control experiments, a prob-
able mechanism for the formation of quinoxaline is given in
Scheme 5. The first step involves p-TSA catalyzed nucleop-
hilic attack of o-phenylenediamine (1) with protonated 10
to give intermediate 11. Elimination of hydrogen sulfide
from 11 forms ketothioimidate 12. In contrast to the result
of the control experiment, H2S is eliminated instead of
methane thiol, probably for the formation of more stable
aromatic quinoxaline ring. Further acid-catalyzed cycliza-
tion of 13 via intermediate 14 through dehydration finally
H
SH
H
S
S
R
S
N
N
S
p-TSA
S
S
R
R
O
R
O
– H2S
O
NH2
NH2
NH2
NH2
O
12
11
2
10
1
N
S
N
S
3
R
R
– H2O
N
H
NH2
OH
O
H
13
14
Scheme 5 Probable mechanism for the formation of quinoxalines
H
N
H
S
S
R
SH
S
S
S
R
N
SH
R
p-TSA
NH2
OH
O
O
OH
R
OH
O
O
10
15
16
2
4
H
S
H
N
H
H
S
R
N
p-TSA
R
N
5
R
OH
O
OH
O
SH
O
O
19
18
17
Scheme 6 Probable mechanism for the formation of benzoxazoles
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–J

E
K. R. Kiran et al.
Paper
Synthesis
washed with hexane, and dried. Salt 7 (10 mmol) and sulfur (2.5
mmol) were stirred in a mixture of DMSO (50 mL) and DMF (20 mL).
The reaction mixture was cooled to 0 °C and triethylamine (2.75 mL)
was added slowly and stirring was continued for 45 min. Ice-cold wa-
ter (50 mL) was added and the mixture was washed with diethyl
ether (25 mL). Methyl iodide (1.25 mL) was added to the aqueous
phase and stirring was continued for 10 min. The product was ex-
tracted with diethyl ether/cyclohexane (50 mL/50 mL, twice) and
dried over anhydrous sodium sulfate. The solvent was evaporated un-
der reduced pressure and the product was purified by column chro-
matography (hexane/EtOAc, 19:1).
Synthesis of Quinoxalines 3; General Procedure
A solution of o-phenyl diamine 1 (1 mmol), oxodithioester 2 (1 mmol)
and p-TSA (0.1 mmol) in toluene (3 mL) was heated at 80 °C for 1 h
and the progress of the reaction was monitored by TLC. Upon comple-
tion of the reaction, the mixture was cooled to r.t., and the reaction
was quenched with ice-cold water (25 mL). The mixture was extract-
ed with EtOAc (3 × 25 mL) and the combined organic layer was
washed with brine (25 mL), dried over anhydrous Na2SO4, and evapo-
rated under vacuum to give the crude quinoxaline 3, which was puri-
fied by column chromatography (hexane/EtOAc, 19:1).
Figure 2 Binding of (a) 3h with human dual-specificity tyrosine-phos-
phorylation-regulated kinase 1A; (b) 3a with human dual-specificity ty-
rosine-phosphorylation-regulated kinase 1A; (c) 5c with human
carboxylesterase, and (d) 5e with human carboxylesterase.
Synthesis of Benzoxazoles 5; General Procedure
In summary, we have reported an acid-catalyzed highly
regioselective cyclization of o-phenylenediammines and o-
aminophenols with -oxodithioesters to form 2-meth-
ylthio-3-aryl/heteroarylquinoxalines and 2-acylbenzoxaz-
oles. In a control reaction, aniline reacted in a highly regi-
oselectively manner with the thiocarbonyl group of -oxo-
dithioester. Probable mechanisms for the formation of
quinoxalines and benzoxazoles are proposed. Furthermore,
biological target prediction of the synthesized molecules
indicated that quinoxalines have good binding affinity to-
wards human dual-specificity tyrosine-phosphorylation-
regulated kinase 1A and benzoxazoles with human carbox-
yl esterase.
A solution of o-amino phenol 4 (1 mmol), oxodithioester 2 (1 mmol)
and p-TSA (0.1 mmol) in toluene (3 mL) was heated at 80 °C for 2 h
and the progress of the reaction was monitored by TLC. Soon after its
completion, the mixture was cooled to r.t., ice-cold water (25 mL) was
added, and the mixture was extracted with EtOAc (3 × 25 mL). The
combined organic layer was washed with a saturated solution of NaCl
(25 mL), dried over anhydrous Na2SO4, and evaporated under reduced
pressure to give the crude benzoxazole 5, which was purified by col-
umn chromatography (hexane/EtOAc, 19:1).
Synthesis of 2-Oxo-N,2-diphenylethanethioamide 9
A solution of aniline 8 (1 mmol), methyl 2-oxo-2-phenylethanedith-
ioate 2a (1 mmol) and p-TSA (0.1 mmol) in toluene (3 mL) was heated
at 80 °C for 1 h and the progress of the reaction was monitored by
TLC. Upon completion of the reaction, the mixture was cooled to r.t.,
and the reaction was quenched with ice cold water (25 mL). The mix-
ture was extracted with EtOAc (3 × 25 mL), and the combined organic
layer was washed with brine (25 mL), dried over anhydrous Na2SO4
and evaporated under vacuum to give the crude 2-oxo-N,2-dipheny-
lethanethioamide 9, which was purified by column chromatography
(hexane/EtOAc, 17:3).
All reagents were purchased from commercial suppliers and used
without further purification. The reactions were monitored by thin-
layer chromatography (TLC) using pre-coated sheets of silica gel
(Merck 60F254, 0.25 mm thickness) and visualized under UV light.
Melting points were determined with a Selaco melting point appara-
tus and are uncorrected. 1H and 13C NMR spectra were obtained with
a AGILENT NMR spectrometer. Chemical shifts () are given in parts
per million (ppm) using the residue solvent (CDCl3) peak as reference
relative to TMS. Coupling constants (J) are given in Hz. Mass spectral
analysis was performed with a Water-Synapt G2 mass spectrometer.
Single-crystal X-ray diffraction data of the compounds were generat-
ed with a Rigoku SMART Lab model, Japan; which uses Cu source and
works at r.t. in a monochrome beam method. The structure was es-
tablished by full matrix least square methods by using the SHELXS
program.
Methyl 2-Oxo-2-phenylethanedithioate (2a)
Yield: 1294 mg (66%); red liquid.
1H NMR (400 MHz, CDCl3):  = 7.94 (d, J = 1.2 Hz, 2 H, Ar-H), 7.60 (t,
J = 7.6 Hz, 1 H, Ar-H), 7.45 (t, J = 8.0 Hz, 2 H, Ar-H), 2.82 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 231.5, 190.8, 134.3, 132.8, 130.4,
128.8, 18.3.
HRMS (ESI): m/z [M + H]+ calcd for C9H9OS2: 197.0089; found:
197.0096.
Synthesis of -Oxodithioesters 2; General Procedure
Methyl 2-(4-Fluorophenyl)-2-oxoethanedithioate (2b)
The products -oxodithioesters 2a–j were prepared by a slight modi-
fication of the earlier reported protocol.37 A solution of methyl ketone
6 (10 mmol) and iodine (10 mmol) in pyridine (5 mL) was heated at
reflux for 12 h. The pyridinium iodide salt 7 formed was filtered,
Yield: 1278 mg (60%); red liquid.
1H NMR (400 MHz, CDCl3):  = 7.99–7.96 (dd, J = 5.6, 3.2 Hz, 2 H, Ar-
H), 7.11 (t, J = 8.1 Hz, 2 H, Ar-H), 2.81 (s, 3 H, SMe).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–J

F
K. R. Kiran et al.
Paper
Synthesis
13C NMR (100 MHz, CDCl3):  = 230.7, 189.3, 167.7, 165.1 (d,
J = 255.9 Hz), 133.3, 133.2 (d, J = 9.8 Hz), 129.2, 116.0, 115.7 (d,
J = 22.4 Hz), 18.4.
1H NMR (400 MHz, CDCl3):  = 7.92 (d, J = 6.8 Hz, 2 H, Ar-H), 6.91 (d,
J = 9.2 Hz, 2 H, Ar-H), 3.86 (s, 3 H, OMe), 2.80 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 232.1, 190.0, 164.6, 132.9, 125.4,
19F NMR (375 MHz, CDCl3):  = –102.4
113.9, 55.9, 18.3.
HRMS (ESI): m/z [M + H]+ calcd for C9H8FOS2: 214.9995; found:
HRMS (ESI): m/z [M + H]+ calcd for C10H11O2S2: 227.0195; found:
215.0001.
227.0189.
Methyl 2-(4-Chlorophenyl)-2-oxoethanedithioate (2c)
Methyl 2-(Naphthalen-2-yl)-2-oxoethanedithioate (2i)
Yield: 1725 mg (75%); red liquid.
Yield: 2017 mg (82%); red solid; mp 73–75 °C.
1H NMR (400 MHz, CDCl3):  = 7.87 (d, J = 2.0 Hz, 2 H, Ar-H), 7.43 (d,
J = 2.8 Hz, 2 H, Ar-H), 2.82 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 230.3, 189.4, 140.9, 131.8, 131.2,
1H NMR (400 MHz, CDCl3):  = 8.45 (s, 1 H, Ar-H), 8.01 (dd, J = 6.8,
1.6 Hz, 1 H Ar-H), 7.92–7.85 (m, 3 H, Ar-H), 7.63–7.52 (m, 2 H, Ar-H),
2.87 (s, 3 H, SMe).
129.2, 18.4.
13C NMR (100 MHz, CDCl3):  = 231.4, 191.0, 136.1, 133.3, 132.1,
130.1, 129.8, 129.3, 128.5, 127.9, 127.0, 124.8, 18.5.
HRMS (ESI): m/z [M + H]+ calcd for C13H11OS2: 247.0246; found:
HRMS (ESI): m/z [M + H]+ calcd for C9H8ClOS2: 230.9700; found:
230.9709.
247.0243.
Methyl 2-(4-Bromophenyl)-2-oxoethanedithioate (2d)
Methyl 2-Oxo-2-(thiophen-2-yl)ethanedithioate (2j)
Yield: 2137 mg (78%); red liquid.
Yield: 808 mg (40%); red liquid.
1H NMR (400 MHz, CDCl3):  = 7.82 (d, J = 3.2 Hz, 1 H, Ar-H), 7.75 (d,
J = 3.6 Hz, 1 H, Ar-H), 7.12 (t, J = 4.4 Hz, 1 H, Ar-H), 2.77 (s, 3 H, SMe).
1H NMR (400 MHz, CDCl3):  = 7.84 (d, J = 8.4 Hz, 2 H, Ar-H), 7.24 (d,
J = 8.4 Hz, 2 H, Ar-H), 2.81 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 231.7, 190.8, 145.6, 130.6, 130.2,
129.6, 18.4.
13C NMR (100 MHz, CDCl3):  = 228.9, 182.5, 136.8, 132.4, 128.7,
128.4, 18.6.
HRMS (ESI): m/z [M + H]+ calcd for C9H7BrOS2: 274.9200; found:
274.9206.
HRMS (ESI): m/z [M + H]+ calcd for C7H7OS3: 202.9654; found:
202.9660.
Methyl 2-(3-Bromophenyl)-2-oxoethanedithioate (2e)
2-(Methylthio)-3-phenylquinoxaline (3a)
Yield: 1587 mg (69%); red liquid.
Yield: 231 mg (65%); white solid; mp 165–167 °C.
1H NMR (400 MHz, CDCl3):  = 8.06 (s, 1 H, Ar-H), 7.86 (d, J = 8.0 Hz,
1 H, Ar-H), 7.71 (d, J = 8.0 Hz, 1 H, Ar-H), 7.33 (t, J = 8.0 Hz, 1 H, Ar-H),
2.83 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 229.7, 189.0, 137.0, 134.7, 133.0,
130.1, 128.9, 122.7, 18.4.
1H NMR (400 MHz, CDCl3):  = 8.06 (d, J = 8.0 Hz, 1 H, Ar-H), 7.98 (d,
J = 8.4 Hz, 1 H, Ar-H), 7.79–7.77 (dd, J = 4.0, 2.0 Hz, 2 H, Ar-H), 7.67–
7.60 (m, 2 H, Ar-H), 7.51 (t, J = 3.6 Hz, 3 H, Ar-H), 2.63 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 155.5, 153.4, 141.6, 139.3, 137.4,
129.7, 129.7, 129.2, 128.9, 128.4, 128.1, 127.4, 13.7.
HRMS (ESI): m/z [M + H]+ calcd for C15H13N2S: 253.0794; found:
HRMS (ESI): m/z [M + H]+ calcd for C9H8BrOS2: 274.9194; found:
274.9195.
253.0798.
Methyl 2-(4-Nitrophenyl)-2-oxoethanedithioate (2f)
2-(4-Fluorophenyl)-3-(methylthio)quinoxaline (3b)
Yield: 1373 mg (57%); reddish yellow solid; mp 55–57 °C.
Yield; 232 mg (92%); pale-yellow solid; mp 160–162 °C.
1H NMR (400 MHz, CDCl3):  = 8.27 (d, J = 2.0 Hz, 2 H, Ar-H), 8.10 (d,
J = 2.0 Hz, 2 H, Ar-H), 2.85 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 228.6, 187.8, 150.7, 138.0, 131.3,
1H NMR (400 MHz, CDCl3):  = 8.04–7.96 (dd, J = 14.4, 8.0 Hz, 2 H, Ar-
H), 7.68 (t, J = 7.2 Hz, 2 H, Ar-H), 7.70–7.59 (m, 2 H, Ar-H), 7.19 (t,
J = 8.4 Hz, 2 H, Ar-H), 2.64 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 159.6, 157.1, 150.3, 147.0 (d,
J = 331.8 Hz), 136.3, 133.8, 128.1, 125.8, 125.7 (d, J = 7.8 Hz), 124.5,
123.8, 122.9, 122.1, 110.3, 110.1 (d, J = 21.4 Hz), 8.4.
123.6, 18.5.
HRMS (ESI): m/z [M + H]+ calcd for C9H8NO3S2: 241.9940; found:
241.9936.
19F NMR (375 MHz, CDCl3):  = –110.9
Methyl 2-Oxo-2-(p-tolyl)ethanedithioate (2g)
HRMS (ESI): m/z [M + H]+ calcd for C15H12FN2S: 271.0700; found:
Yield: 1449 mg (69%); red liquid.
271.0703.
1H NMR (400 MHz, CDCl3):  = 7.84 (d, J = 8.4 Hz, 2 H, Ar-H), 7.28 (d,
J = 8.4 Hz, 2 H, Ar-H), 2.81 (s, 3 H, SMe), 2.42 (s. 3 H, Ar-Me).
2-(4-Chlorophenyl)-3-(methylthio)quinoxaline (3c)
13C NMR (100 MHz, CDCl3):  = 231.7, 190.8, 145.6, 130.6, 130.2,
129.3, 21.9, 18.4.
Yield: 231 mg (93%); pale-yellow solid; mp 154–155 °C.
1H NMR (400 MHz, CDCl3):  = 8.03–7.96 (dd, J = 12.8, 8.4 Hz, 2 H, Ar-
H), 7.74–7.76 (m, 3 H, Ar-H), 7.63–7.59 (m, 1 H, Ar-H), 7.47 (d,
J = 8.4 Hz, 2 H, Ar-H), 2.63 (s, 3 H, SMe).
HRMS (ESI): m/z [M + H]+ calcd for C10H11OS2: 211.0246; found:
211.0240.
13C NMR (100 MHz, CDCl3):  = 150.2, 146.8, 136.3, 133.8, 130.6,
130.4, 125.1, 124.6, 123.8, 123.4, 122.9, 122.1, 8.4.
Methyl 2-(4-Methoxyphenyl)-2-oxoethanedithioate (2h)
Yield: 2169 mg (96%); red liquid.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–J

G
K. R. Kiran et al.
Paper
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C15H12ClN2S: 287.0404; found:
287.0400.
1H NMR (400 MHz, CDCl3):  = 8.09 (d, J = 4.0 Hz, 1 H, Ar-H), 7.99 (d,
J = 6.4 Hz, 1 H, Ar-H), 7.17 (d, J = 8.0 Hz, 1 H, Ar-H), 7.63–7.52 (m, 3 H,
Ar-H), 7.17 (t, J = 5.2 Hz, 1 H, Ar-H), 2.71 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 154.0, 146.3, 141.3, 140.7, 138.8,
2-(3-Bromophenyl)-3-(methylthio)quinoxaline (3d)
129.6, 129.5, 129.5, 128.8, 128.3, 127.8, 127.3, 13.9.
Yield: 312 mg (94%); white solid; mp 161–168 °C.
HRMS (ESI): m/z [M + H]+ calcd for C13H11N2S2: 258.0285; found:
258.0284.
1H NMR (400 MHz, CDCl3):  = 8.04–7.97 (dd, J = 14.4, 8.0 Hz, 2 H, Ar-
H), 7.92 (s, 1 H, Ar-H), 7.74–7.61 (m, 4 H, Ar-H), 7.38 (t, J = 8.0 Hz, 1 H,
Ar-H), 2.64 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 155.5, 151.8, 141.8, 139.3, 139.1,
6-Bromo-2-(methylthio)-3-phenylquinoxaline (3j)
132.7, 132.1, 130.1, 129.9, 129.2, 128.3, 127.6, 127.5, 122.6, 13.7.
Yield: 310 mg (92%); white solid; mp 160–162 °C.
HRMS (ESI): m/z [M + H]+ calcd for C15H12BrN2S: 330.9899; found:
330.9901.
1H NMR (400 MHz, CDCl3):  = 8.17 (d, J = 2.4 Hz, 1 H, Ar-H), 7.89 (d,
J = 8.8 Hz, 1 H, Ar-H), 7.76–7.67 (m, 3 H, Ar-H), 7.51 (t, J = 3.2 Hz, 3 H,
Ar-H), 2.60 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 152.0, 148.4, 136.7, 132.6, 131.6,
2-(Methylthio)-3-(4-nitrophenyl)quinoxaline (3e)
126.1, 125.2, 124.6, 124.5, 123.5, 123.1, 118.3, 8.5.
Yield: 320 mg (89%); pale-yellow solid; mp 184–185 °C.
HRMS (ESI): m/z [M + H]+ calcd for C15H12BrN2S: 329.9826; found:
1H NMR (400 MHz, CDCl3):  = 8.37 (d, J = 8.4 Hz, 2 H, Ar-H), 8.05–
329.9827.
7.98 (m, 4 H, Ar-H), 7.76–7.64 (m, 2 H, Ar-H), 2.67 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 144.9, 140.9, 138.4, 133.5, 131.8,
129.0, 120.6, 120.2, 119.2, 118.5, 117.5, 113.5, 7.2.
3-(Methylthio)-2-phenyl-6-(trifluoromethyl)quinoxaline (3k)
Yield: 180 mg (55%); white solid; mp 126–128 °C.
HRMS (ESI): m/z [M + H]+ calcd for C15H12N3O2S: 298.0645; found:
298.0650.
1H NMR (400 MHz, CDCl3):  = 8.32 (s, 1 H, Ar-H), 8.18 (d, J = 12.0 Hz,
1 H, Ar-H), 7.82 (d, J = 8 Hz, 3 H, Ar-H), 7.57 (s, 3 H, Ar-H), 2.68 (s, 3 H,
SMe).
2-(Methylthio)-3-(p-tolyl)quinoxaline (3f)
13C NMR (100 MHz, CDCl3):  = 158.0, 155.4, 140.6, 140.4, 136.7,
130.3, 130.1, 128.9, 128.7, 128.5, [125.3, 125.3, 125.1 (multiplet)],
122.4, 13.9.
Yield: 369 mg (93%); white solid; mp 106–108 °C.
1H NMR (400 MHz, CDCl3):  = 8.04–8.02 (dd, J = 7.2 Hz, 1.2 Hz, 2 H,
Ar-H), 7.70–7.60 (m, 4 H, Ar-H), 7.31 (d, J = 7.6 Hz, 2 H, Ar-H), 2.62 (s,
3 H, SMe), 2.43 (s, 3 H, Ar-Me).
19F NMR (375 MHz, CDCl3):  = –62.5
HRMS (ESI): m/z [M + H]+ calcd for C15H12BrN2S: 321.0595; found:
13C NMR (100 MHz, CDCl3):  = 150.6, 148.2, 136.2, 134.5, 133.9,
321.0589.
129.2, 124.1, 123.8, 123.7, 123.5, 122.6, 122.1, 16.1, 8.4.
HRMS (ESI): m/z [M + H]+ calcd for C16H15N2S: 267.0950; found:
267.0955.
(5-Nitrobenzo[d]oxazol-2-yl)(phenyl)methanone (3l)
Yield: 176 mg (58%); white solid; mp 188–190 °C.
1H NMR (400 MHz, CDCl3):  = 8.90 (s, 1 H, Ar-H), 8.19 (d, J = 8.0 Hz,
1 H, Ar-H), 7.85 (t, J = 4.0 Hz, 1 H, Ar-H), 7.58 (d, J = 8.0 Hz, 2 H, Ar-H),
7.57 (s, 3 H, Ar-H), 2.69 (s, 3 H, SMe).
13C NMR (100 MHz, CDCl3):  = 159.3, 156.3, 147.7, 141.9, 140.4,
136.3, 130.6, 130.4, 129.0, 128.8, 123.6, 121.5, 14.05.
2-(4-Methoxyphenyl)-3-(methylthio)quinoxaline (3g)
Yield: 217 mg (87%); white solid; mp 135–137 °C.
1H NMR (400 MHz, CDCl3):  = 8.02–7.94 (dd, J = 20.0, 7.2 Hz, 2 H, Ar-
H), 7.75–7.59 (m, 4 H, Ar-H), 7.02 (d, J = 6.8 Hz, 2 H, Ar-H), 3.86 (s,
3 H, OMe), 2.62 (s, 3 H, SMe).
HRMS (ESI): m/z [M + H]+ calc for C15H12BrN2S: 298.3320; found:
13C NMR (100 MHz, CDCl3):  = 155.5, 150.6, 147.8, 136.1, 133.9,
298.3318.
125.2, 124.4, 124.1, 123.7, 122.7, 122.0, 108.5, 50.0, 8.5.
HRMS (ESI): m/z [M + H]+ calcd for C16H15N2OS: 282.0827; found:
282.0830.
Benzo[d]oxazol-2-yl(phenyl)methanone (5a)
Yield: 171 mg (75%); pale-yellow solid; mp 124–126 °C.
1H NMR (400 MHz, CDCl3):  = 8.55 (d, J = 8.0 Hz, 2 H, Ar-H), 7.94 (d,
J = 8.0 Hz, 1 H, Ar-H), 7.71–7.66 (dd, J = 7.6, 7.2 Hz, 2 H, Ar-H), 7.58–
7.44 (m, 4 H, Ar-H).
13C NMR (100 MHz, CDCl3):  = 180.6, 157.1, 150.4, 140.7, 135.0,
134.3, 131.0, 128.6, 128.4, 125.7, 122.4, 11.6.
2-(Methylthio)-3-(naphthalen-1-yl)quinoxaline (3h)
Yield: 206 mg (84%); pale-yellow solid; mp 128–130 °C.
1H NMR (400 MHz, CDCl3):  = 8.3 (s, 1 H, Ar-H), 8.09–7.85 (m, 6 H,
Ar-H), 7.70 (t, J = 7.6 Hz, 1 H, Ar-H), 7.63 (t, J = 7.6 Hz, 1 H, Ar-H),
7.57–7.51 (m, 2 H, Ar-H), 2.65 (s, 3 H, SMe).
HRMS (ESI): m/z [M + H]+ calcd for C14H10NO2: 223.0633; found:
223.0632.
13C NMR (100 MHz, CDCl3):  = 150.7, 148.0, 136.3, 134.0, 129.4,
128.5, 127.6, 124.5, 123.9, 123.6, 123.3, 122.9, 122.8, 122.4, 122.1,
121.6, 121.1, 120.8, 8.7.
HRMS (ESI): m/z [M + H]+ calcd for C19H15N2S: 302.0878; found:
Benzo[d]oxazol-2-yl(4-fluorophenyl)methanone (5b)
302.0880.
Yield: 176 mg (78%); pale-yellow solid; mp 116–118 °C.
1H NMR (400 MHz, CDCl3):  = 8.67–8.63 (dd, J = 5.2, 3.6 Hz, 2 H, Ar-
H), 7.93 (d, J = 7.6 Hz, 1 H, Ar-H), 7.70 (d, J = 8.4 Hz, 1 H, Ar-H), 7.55 (t,
J = 7.6 Hz, 1 H, Ar-H), 7.48 (d, J = 8.0 Hz, 1 H, Ar-H), 7.25–7.21 (dd,
J = 5.6, 3.2 Hz, 2 H, Ar-H).
2-(Methylthio)-3-(thiophen-2-yl)quinoxaline (3i)
Yield: 230 mg (90%); pale-yellow solid; mp 145–147 °C.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–J

H
K. R. Kiran et al.
Paper
Synthesis
13C NMR (100 MHz, CDCl3):  = 173.3, 162.5, 159.9 (d, J = 256.8 Hz),
151.5, 145.0, 135.3, 128.6, 128.5 (d, J = 9.7 Hz), 125.9, 123.2, 120.4,
117.0, 110.6, 110.4 (d, J = 22.3 Hz), 106.5.
HRMS (ESI): m/z [M + H]+ calcd for C15H12NO3: 254.0812; found:
254.0813.
19F NMR (375 MHz, CDCl3):  = –102.6.
Benzo[d]oxazol-2-yl(thiophen-2-yl)methanone (5h)
HRMS (ESI): m/z [M + H]+ calcd for C14H9FNO2: 241.0539; found:
Yield: 186 mg (82%); yellow solid; mp 120–122 °C.
1H NMR (400 MHz, CDCl3):  = 8.72 (d, J = 3.6 Hz, 1 H, Ar-H), 7.92 (d,
J = 8.0 Hz, 1 H, Ar-H), 7.83 (d, J = 3.2 Hz, 1 H, Ar-H), 7.68 (d, J = 8.4 Hz,
1 H, Ar-H), 7.54–7.43 (m, 2 H, Ar-H), 7.24 (t, J = 4.4 Hz, 1 H, Ar-H).
241.0543.
Benzo[d]oxazol-2-yl(4-chlorophenyl)methanone (5c)
Yield: 179 mg (80%); pale-yellow solid; mp 110–112 °C.
13C NMR (100 MHz, CDCl3):  = 166.8, 151.4, 145.2, 135.3, 135.2,
132.2, 131.7, 123.4, 123.0, 120.4, 116.9, 106.5.
HRMS (ESI): m/z [M + H]+ calcd for C12H8NO2S: 230.0270; found:
230.0275.
1H NMR (400 MHz, CDCl3):  = 8.51 (d, J = 8.8 Hz, 2 H, Ar-H), 7.89 (d,
J = 8.4 Hz, 1 H, Ar-H), 7.66 (d, J = 8.0 Hz, 1 H, Ar-H), 7.45–7.42 (m, 4 H,
Ar-H).
13C NMR (100 MHz, CDCl3):  = 173.7, 151.4, 145.0, 135.7, 135.3,
127.8, 127.1, 123.6, 123.3, 120.5, 117.0, 106.5.
(5-Methylbenzo[d]oxazol-2-yl)(phenyl)methanone (5i)
HRMS (ESI): m/z [M + H]+ calcd for C14H9ClNO2: 258.0316; found:
Yield: 198 mg (82%); pale-yellow solid; mp 126–128 °C.
1H NMR (400 MHz, CDCl3):  = 8.51 (t, J = 7.6 Hz, 2 H, Ar-H), 7.70–7.65
(m, 2 H, Ar-H), 7.58–7.53 (m, 3 H, Ar-H), 7.36–7.33 (dd, J = 7.2, 1.2 Hz,
1 H, Ar-H), 2.50 (s, 3 H. Me).
258.0320.
Benzo[d]oxazol-2-yl(3-bromophenyl)methanone (5d)
Yield: 184 mg (84%); pale-yellow solid; mp 123–125 °C.
13C NMR (100 MHz, CDCl3):  = 180.6, 157.2, 148.7, 140.9, 135.8,
135.1, 134.2, 130.9, 129.9, 128.6, 121.9, 111.2, 21.6.
HRMS (ESI): m/z [M + H]+ calcd for C15H12NO2: 238.0863; found:
238.0861.
1H NMR (400 MHz, CDCl3):  = 8.68 (s, 1 H, Ar-H), 8.53 (d, J = 8.0 Hz,
1 H, Ar-H), 7.96 (d, J = 8.4 Hz, 1 H, Ar-H), 7.79 (d, J = 8.0 Hz, 1 H, Ar-H),
7.70 (d, J = 8.4 Hz, 1 H, Ar-H), 7.55 (t, J = 7.6 Hz, 1 H,Ar-H), 7.49–7.41
(m, 2 H, Ar-H).
13C NMR (100 MHz, CDCl3):  = 173.6, 151.3, 145.1, 135.3, 131.7,
4-Methoxyphenyl(5-methylbenzo[d]oxazol-2-yl)methanone (5j)
131.2, 128.4, 124.8, 124.3, 123.4, 120.5, 117.4, 117.2, 106.5.
Yield: 187 mg (79%); pale-yellow solid; mp 134–136 °C.
HRMS (ESI): m/z [M + H]+ calcd for C14H9BrNO2: 301.9811; found:
301.9805.
1H NMR (400 MHz, CDCl3):  = 8.59 (d, J = 9.2 Hz, 2 H, Ar-H), 7.69 (s,
1 H, Ar-H), 7.56 (d, J = 8.4 Hz, 1 H, Ar-H), 7.33 (d, J = 8.0 Hz, 1 H, Ar-H),
7.03 (d, J = 8.8 Hz, 2 H, Ar-H), 3.91 (s, 3 H, OMe), 2.51 (s, 3 H, Ar-Me).
13C NMR (100 MHz, CDCl3):  = 178.8, 164.6, 157.9, 148.4, 141.0,
Benzo[d]oxazol-2-yl(4-nitrophenyl)methanone (5e)
Yield: 191 mg (86%); pale-yellow solid; mp 142–144 °C.
135.6, 133.6, 129.5, 128.1, 121.7, 113.9, 111.1, 55.5, 21.5.
1H NMR (400 MHz, CDCl3):  = 8.76 (d, J = 9.2 Hz, 2 H, Ar-H), 8.39 (d,
J = 8.8 Hz, 2 H, Ar-H), 7.96 (d, J = 8.0 Hz, 1 H, Ar-H), 7.73 (d, J = 8.4 Hz,
1 H, Ar-H), 7.61–7.57 (m, 1 H, Ar-H), 7.50 (t, J = 7.2 Hz, 1 H, Ar-H).
HRMS (ESI): m/z [M + H]+ calcd for C15H12NO3: 268.0968; found:
268.0970.
13C NMR (100 MHz, CDCl3):  = 173.4, 151.1, 145.4, 145.2, 135.3,
(5-Methylbenzo[d]oxazol-2-yl)(thiophen-2-yl)methanone (5k)
134.1, 126.8, 123.9, 120.8, 118.3, 117.3, 106.6.
Yield: 80%(192 mg); yellow solid; mp 132–135 °C.
HRMS (ESI): m/z [M + H]+ calcd for C14H9N2O4: 269.0557; found:
269.0560.
1H NMR (400 MHz, CDCl3):  = 8.68 (d, J = 3.6 Hz, 1 H, Ar-H), 7.80 (d,
J = 4.8 Hz, 1 H, Ar-H), 7.66 (s, 1 H, Ar-H), 7.52 (d, J = 8.4 Hz, 1 H, Ar-H),
7.30 (d, J = 8.4 Hz, 1 H, Ar-H), 7.22 (t, J = 4.4 Hz, 1 H, Ar-H), 2.47 (s,
3 H, Me).
Benzo[d]oxazol-2-yl(p-tolyl)methanone (5f)
Yield: 169 mg (75%); pale-yellow solid; mp 116–118 °C.
13C NMR (100 MHz, CDCl3):  = 166.8, 151.6, 143.5, 135.5, 135.3,
132.1, 131.5, 130.4, 124.4, 123.3, 116.5, 105.8, 16.1.
HRMS (ESI): m/z [M + H]+ calcd for C13H10NO2S: 244.0427; found:
244.0430.
1H NMR (400 MHz, CDCl3):  = 8.44 (d, J = 8.4 Hz, 2 H, Ar-H), 7.92 (d,
J = 8.0 Hz, 1 H, Ar-H), 7.68 (d, J = 8.4 Hz, 1 H, Ar-H), 7.54–7.44 (m, 2 H,
Ar-H), 7.34 (d, J = 8.4 Hz, 2 H, Ar-H), 2.45 (s, 3 H, Ar-Me).
13C NMR (100 MHz, CDCl3):  = 174.8, 151.9, 145.0, 140.2, 135.4,
127.1, 125.8, 124.0, 122.9, 120.3, 116.9, 106.5, 16.5.
(5-Nitrobenzo[d]oxazol-2-yl)(phenyl)methanone (5l)
HRMS (ESI): m/z [M + H]+ calcd for C15H12NO2: 238.2655; found:
Yield: 123 mg (45%); yellow solid; mp 138–140 °C.
1H NMR (400 MHz, CDCl3):  = 8.89 (s, 1 H, Ar-H), 8.59–8.51 (m, 3 H,
Ar-H), 7.87 (d, J = 9.2 Hz, 1 H, Ar-H), 7.76 (t, J = 7.2 Hz, 1 H, Ar-H), 7.62
(t, J = 7.6 Hz, 2 H, Ar-H).
238.2657.
Benzo[d]oxazol-2-yl(4-methoxyphenyl)methanone (5g)
Yield: 172 mg (77%); pale-yellow solid; mp 126–128 °C.
13C NMR (100 MHz, CDCl3):  = 174.8, 154.5, 148.8, 141.3, 136.2,
130.2, 129.6, 126.3, 124.1, 119.1, 114.1, 107.6.
HRMS (ESI): m/z [M + H]+ calcd for C14H9N2O4: 269.0485; found:
269.0490.
1H NMR (400 MHz, CDCl3):  = 8.58 (d, J = 7.6 Hz, 2 H, Ar-H), 7.91 (d,
J = 7.6 Hz, 1 H, Ar-H), 7.68 (d, J = 8.0 Hz, 1 H, Ar-H), 7.53–7.42 (m, 2 H,
Ar-H), 7.01 (d, J = 8.4 Hz, 2 H, Ar-H), 3.90 (s, 3 H, OMe).
13C NMR (100 MHz, CDCl3):  = 173.4, 159.3, 152.1, 145.0, 135.4,
128.2, 122.7, 122.6, 120.2, 116.8, 108.6, 106.4, 50.2.
2-Oxo-N,2-diphenylethanethioamide (9)
Yield: 160 mg (65%); orange red solid; mp 140–142 °C.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–J

I
K. R. Kiran et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3):  = 9.80–10.60 (br s, 1 H, NH), 8.05–7.94
(m, 4 H, Ar-H), 7.58–7.19 (m, 6 H, Ar-H).
13C NMR (100 MHz, CDCl3):  = 184.7, 181.7, 132.5, 128.4, 125.5,
Dendle, M. T. A.; Sacchettini, J. C.; Kelly, J. W. Angew. Chem. Int.
Ed. 2003, 42, 2758. (i) Bryson, H. M.; Fulton, B.; Benfield, P.
Drugs 1996, 52, 549.
(3) (a) Sonawane, N. D.; Rangnekar, D. W. J. Heterocycl. Chem. 2002,
39, 303. (b) Dailey, S.; Feast, W. J.; Peace, R. J.; Sage, I. C.; Till, S.;
Wood, E. L. J. Mater. Chem. 2001, 11, 2238. (c) O’Brien, D.;
Weaver, M. S.; Lidzey, D. G.; Bradley, D. D. C. Appl. Phys. Lett.
1996, 69, 881.
123.8, 123.4, 122.8, 121.9, 116.9.
HRMS (ESI): m/z [M + H]+ calcd for C14H12NOS: 241.0561; found:
241.0568.
(4) (a) Bhosale, R. S.; Sarda, S. R.; Ardhapure, S. S.; Jadhav, W. N.;
Bhusare, S. R.; Pawar, R. P. Tetrahedron Lett. 2005, 46, 7183.
(b) Cai, J. J.; Zou, J. P.; Pan, X.-Q.; Zhang, W. Tetrahedron Lett.
2008, 49, 7386. (c) More, S. V.; Sastry, M.; Yao, C. F. Green Chem.
2006, 8, 91. (d) Kadam, H. K.; Khan, S.; Kunkalkar, R. A.; Tilve, S.
G. Tetrahedron Lett. 2013, 54, 1003. (e) Kumar, D.; Seth, K.;
Kommi, D. N.; Bhagat, S.; Chakraborti, A. K. RSC Adv. 2013, 3,
15157. (f) Kumbhar, A.; Kamble, S.; Barge, M.; Rashinkar, G.;
Salunkhe, R. Tetrahedron Lett. 2012, 53, 2756. (g) Bachhav, H.
M.; Bhagat, S. B.; Telvekar, V. N. Tetrahedron Lett. 2011, 52, 5697.
(h) Harsha, K. B.; Shobith, R.; Preetham, H. D.; Swaroop, T. R.;
Gilandoust, M.; Rakesh, K. S.; Rangappa, K. S. ChemistrySelect
2018, 3, 5228.
Funding Information
Authors are grateful to the University Grants Commission-Special As-
sistance Programme, Departmental Research Support (UGC-SAP DRS
III) for providing financial support.
U
n
i
v
ersityGrants
C
o
m
m
i
si
o
n
■
■
o
k
?
■
■
(F.5
4
0/10/D
R
S-
I
/2
0
1
6(S
A
P-I
)
Acknowledgment
Authors are grateful to the IOE for use of the instrumentation facility.
Supporting Information
(5) (a) Raw, S. A.; Wilfred, C. D.; Taylor, R. J. K. Chem. Commun. 2003,
18, 2286. (b) Sithambaram, S.; Ding, Y.; Li, W.; Shen, X.;
Gaenzler, F.; Suib, S. L. Green Chem. 2008, 10, 1029.
(c) Akkilagunta, V. K.; Reddy, V. P.; Kakulapati, R. R. Synlett
2010, 2571. (d) Bhattacharya, T.; Sarma, T. K.; Samanta, S. Catal.
Sci. Technol. 2012, 2, 2216. (e) Kamal, A.; Babu, K. S.; Faazil, S.;
Hussaini, S. M. A.; Shaik, A. B. RSC Adv. 2014, 4, 46369.
(6) Antoniottia, S.; Dunach, E. Tetrahedron Lett. 2002, 43, 3971.
(7) Shi, S.; Wang, T.; Yang, W.; Rudolph, M.; Hashmi, A. S. K. Chem.
Eur. J. 2013, 19, 6576.
(8) (a) Nakhate, A. V.; Rasal, K. B.; Deshmukh, G. P.; Gupta, S. S. R.;
Mannepalli, L. K. J. Chem. Sci. 2017, 129, 1761. (b) Wang, W.;
Shen, Y.; Meng, X.; Zhao, M.; Chen, Y.; Chen, B. Org. Lett. 2011,
13, 4514.
(9) Cho, Y. H.; Kim, K. H.; Cheon, C. H. J. Org. Chem. 2014, 79, 901.
(10) Qi, C.; Jiang, H.; Huang, L.; Chen, Z.; Chen, H. Synthesis 2011,
387.
(11) Zhang, R.; Qin, Y.; Zhang, L.; Luo, S. Org. Lett. 2017, 19, 5629.
(12) Shen, J.; Wang, X.; Lin, X.; Yang, Z.; Cheng, G.; Cui, X. Org. Lett.
2016, 18, 1378.
(13) Yuan, H.; Li, K.; Chen, Y.; Wang, Y.; Cui, J.; Chen, B. Synlett 2013,
24, 2315.
(14) Chen, T.; Chen, X.; Wei, J.; Lin, D.; Xie, Y.; Zeng, W. Org. Lett.
2016, 18, 2078.
(15) Go, A.; Lee, G.; Kim, J.; Bae, S.; Lee, B. M.; Kim, B. H. Tetrahedron
2015, 71, 1215.
(16) Venkatesh, C.; Singh, B.; Mahata, P. K.; Ila, H.; Junjappa, H. Org.
Lett. 2005, 7, 2169.
(17) (a) Wu, Z.; Ede, N. J. Tetrahedron Lett. 2001, 42, 8115. (b) Lee, J.;
Murray, W. V.; Rivero, R. A. J. Org. Chem. 1997, 62, 3874.
(c) Holland, R. J.; Hardcastle, I. R.; Jarman, M. Tetrahedron Lett.
2002, 43, 6435.
(18) McNab, H. J. Chem. Soc., Perkin Trans. 1 1982, 1941.
(19) (a) Xekoukoulotakis, N. P.; Hadjiantoniou-Maroulis, C. P.;
Maroulis, A. J. Tetrahedron Lett. 2000, 41, 10299. (b) Maroulis, A.
J.; Domzaridou, K. C.; Hadjiantoniou-Maroulis, C. P. Synthesis
1998, 1769. (c) Rahman, A.; Ila, H.; Junjappa, H. J. Chem. Soc.,
Chem. Commun. 1984, 430. (d) Makino, K.; Sakata, G.;
Morimoto, K. Heterocycles 1985, 23, 2069.
(20) Gorepatil, P. B.; Mane, Y. D.; Ingle, V. S. Synlett 2013, 24, 2241.
(21) Neumann, K. T.; Lindhardt, A. T.; Bang-Andersen, B.; Skrydstrup,
T. Org. Lett. 2015, 17, 2094.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690616.
S
u
p
p
orit
n
gInformati
o
n
S
u
p
p
orti
n
gInformati
o
n
References
(1) (a) Seitz, L. E.; Suling, W. J.; Reynolds, R. C. J. Med. Chem. 2002,
45, 5604. (b) Gazit, A.; App, H.; McMahon, G.; Chen, J.; Levitzki,
A.; Bohmer, F. D. J. Med. Chem. 1996, 3, 2170. (c) Monge, A.;
Palop, J. A.; Del Castillo, J. C.; Caldero, J. M.; Roca, J.; Romero, G.;
Del Rio, J.; Lasheras, B. J. Med. Chem. 1993, 36, 2745. (d) Boger, D.
L.; Sato, H.; Lerner, A. E.; Hedrick, M. P.; Fecik, R. A.; Miyauchi,
H.; Wilkie, G. D.; Austin, B. J.; Patricelli, M. P.; Cravatt, B. F. Proc.
Natl. Acad. Sci. U. S. A. 2000, 97, 5044. (e) Seierstad, M.;
Breitenbucher, J. G. J. Med. Chem. 2008, 51, 7327. (f) Mcgrath, M.
E.; Sprengeler, P. A.; Hill, C. M.; Martichonok, V.; Cheung, H.;
Somoza, J. R.; Palmer, J. T.; Janc, J. W. Biochemistry 2003, 42,
15018. (g) Tully, D. C.; Vidal, A.; Chatterjee, A. K.; Williams, J. A.;
Roberts, M. J.; Petrassi, H. M.; Sparggon, G.; Bursulaya, B.;
Pacoma, R.; Shipway, A.; Schumacher, A. M.; Danahay, H.;
Harris, J. L. Bioorg. Med. Chem. Lett. 2008, 18, 5895. (h) Zirngibl,
L. Antifungal azoles: a comprehensive survey of their structures
and properties; Wiley-VCH: Weinheim, 1998. (i) Katritzky, A. R.;
Rees, C. W.; Scriven, E. F. Comprehensive Heterocyclic Chemistry
II; Pergamon Press: New York, USA, 4, 1–126, 1996.
(j) Katritzky, A. R.; Pozharskii, A. F. A Handbook of Heterocyclic
Chemistry, 2nd edn., Pergamon, Oxford, 2002. (k) Horton, D. A.;
Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893.
(2) (a) Wu, Z.; Ede, N. J. Tetrahedron Lett. 2001, 42, 8115. (b) Lee, J.;
Murray, W. V.; Rivero, R. A. J. Org. Chem. 1997, 62, 3874.
(c) Holland, R. J.; Hardcastle, I. R.; Jarman, M. Tetrahedron Lett.
2002, 43, 6435. (d) Krchnak, V.; Smith, J.; Vagner, J. Tetrahedron
Lett. 2000, 41, 2835. (e) Johnson, S. M.; Connelly, S.; Wilson, I.
A.; Kelly, J. W. J. Med. Chem. 2008, 51, 260. (f) Davidson, J. P.;
Corey, E. J. J. Am. Chem. Soc. 2003, 125, 1348. (g) Ueki, M.; Ueno,
K.; Miyadoh, S.; Abe, K.; Shibata, K.; Taniguchi, M.; Oi, S. J.
J. Antibiot. 1993, 46, 1089. (h) Razavi, H.; Palaninathan, K.;
Powers, E. T.; Wiseman, R. L.; Purkey, H. E.;
Mohamedmohaideen, N. N.; Deechongkit, S.; Chiang, K. P.;
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–J

J
K. R. Kiran et al.
Paper
Synthesis
(22) Mayo, M. S.; Yu, X.; Zhou, X.; Feng, X.; Yamamoto, Y.; Bao, M.
J. Org. Chem. 2014, 79, 6310.
(37) (a) Moran, J. R.; Tapia, I.; Alcazar, V. Tetrahedron 1990, 46, 1783.
(b) Villemin, D.; Thibault-Starzyk, F. Synlett 1992, 148.
(38) Vedejs, E.; Arnost, M. J.; Dolphin, J. M.; Eustache, J. J. Org. Chem.
1980, 45, 2601.
(39) Mloston, G.; Urbaniak, K.; Gulea, M.; Masson, S.; Linden, A.;
Heimgartner, H. Helv. Chim. Acta 2005, 88, 2582.
(23) Bastug, G.; Eviolitte, C.; Markó, I. E. Org. Lett. 2012, 14, 3502.
(24) Seijas, J. A.; Vázquez-Tato, M. P.; Carballido-Reboredo, M. R.;
Crecente-Campo, J.; Romar-López, L. Synlett 2007, 313.
(25) Nguyen, T. B.; Retailleau, P. Org. Lett. 2017, 19, 3887.
(26) Liu, B.; Yin, M.; Gao, H.; Wu, W.; Jiang, H. J. Org. Chem. 2013, 78,
3009.
(27) (a) Saha, P.; Ramana, T.; Purkait, N.; Ali, M. A.; Paul, R.;
Punniyamurthy, T. J. Org. Chem. 2009, 74, 8719. (b) Yang, D.;
Zhu, X.; Wei, W.; Jiang, M.; Zhang, N.; Ren, D.; You, J.; Wang, H.
Synlett 2014, 25, 729. (c) Evindar, G.; Batey, R. A. J. Org. Chem.
2006, 71, 1802.
(28) Chen, C. Y.; Andreani, T.; Li, H. Org. Lett. 2011, 13, 6300.
(29) Guru, M. M.; Ali, M. A.; Punniyamurthy, T. Org. Lett. 2011, 13,
1194.
(30) Srivastava, V. P.; Yadav, L. D. S. Synlett 2013, 24, 2758.
(31) (a) Hinsberg, O. Ber. Dtsch. Chem. Ges. 1884, 17, 318.
(b) Hinsberg, O. Justus Liebigs Ann. Chem. 1887, 327. (c) Körner,
G. Ber. Dtsch. Chem. Ges. 1884, 17, 572.
(32) (a) Singh, D. P.; Deivedi, S. K.; Hashim, S. R.; Singhal, R. G. Phar-
maceuticals 2010, 3, 2416. (b) Yuan, H.; Li, X.; Qu, X.; Sun, L.; Xu,
W.; Tang, W. Med. Chem. Res. 2009, 18, 671.
(33) Fan, X.; He, Y.; Zhang, X.; Guo, S.; Wang, Y. Tetrahedron 2011, 67,
6369.
(34) Cui, L.; He, Y.; Fan, X. Chin. J. Chem. 2012, 30, 992.
(35) Boominathan, S. S. K.; Hu, W. P.; Senadi, G. C.; Vandavasia, J. K.;
Wang, J. J. Chem. Commun. 2014, 50, 6726.
(36) (a) Wu, X. F.; Anbarasan, A.; Neumann, H.; Beller, M. Angew.
Chem. Int. Ed. 2010, 49, 7316. (b) Yang, K.; Cheng, Z.; Wang, P.;
Zhang, Y.; Ge, H. Chem. Eur. J. 2014, 20, 7241. (c) Harn, N. K.;
Gramer, C. J.; Anderson, B. A. Tetrahedron Lett. 1995, 36, 9453.
(d) Toh, Q. Y.; McNally, A.; Vera, S.; Erdmann, N.; Gaunt, M. J.
J. Am. Chem. Soc. 2013, 135, 3772. (e) Wu, X. F.; Anbarasan, P.;
Neumann, H.; Beller, M. Angew. Chem. Int. Ed. 2010, 49, 7316.
(40) (a) Anil, S. M.; Shobith, R.; Kiran, K. R.; Swaroop, T. R.; Mallesha,
N.; Sadashiva, M. P. New J. Chem. 2019, 43, 182.
(b) Bommegowda, Y. K.; Lingaraju, G. S.; Thamas, S.; Kumar, K. S.
V.; Kumara, C. S. P.; Rangappa, K. S.; Sadashiva, M. P. Tetrahedron
Lett. 2013, 54, 2693. (c) Bommegowda, Y. K.; Mallesha, N.;
Vinayaka, A. C.; Sadashiva, M. P. Chem. Lett. 2015, 45, 268.
(d) Kumar, K. S. V.; Swaroop, T. R.; Rajeev, N.; Vinayaka, A. C.;
Lingaraju, G. S.; Rangappa, K. S.; Sadashiva, M. P. Synlett 2016,
27, 1363. (e) Vinayaka, A. C.; Sadashiva, M. P.; Wu, X.; Biryukov,
S. S.; Stoute, J. A.; Rangappa, K. S.; Gowda, D. C. Org. Biomol.
Chem. 2014, 12, 8555. (f) Rajeev, N.; Swaroop, T. R.; Anil, S. M.;
Kiran, K. R.; Rangappa, K. S.; Sadashiva, M. P. J. Chem. Sci. 2018,
130, 150.
(41) (a) Lingaraju, G. S.; Swaroop, T. R.; Vinayaka, A. C.; Kumar, K. S.
S.; Sadashiva, M. P.; Rangappa, K. S. Synthesis 2012, 44, 1373.
(b) Swaroop, T. R.; Roopashree, R.; Ila, H.; Rangappa, K. S. Tetra-
hedron Lett. 2013, 54, 147. (c) Swaroop, T. R.; Ila, H.; Rangappa,
K. S. Tetrahedron Lett. 2013, 54, 5288. (d) Raghava, B.;
Parameshwarappa, B.; Acharya, A.; Swaroop, T. R.; Rangappa, K.
S.; Ila, H. Eur. J. Org. Chem. 2014, 1882. (e) Vinayaka, A. C.;
Swaroop, T. R.; Chikkade, P. K.; Rangappa, K. S.; Sadashiva, M. P.
RSC Adv. 2016, 6, 11528. (f) Rajeev, N.; Swaroop, T. R.; Anil, S.
M.; Bommegowda, Y. K.; Rangappa, K. S.; Sadashiva, M. P.
Synlett 2017, 28, 2281.
(42) (a) Gfeller, D.; Michielin, O.; Zoete, V. Bioinformatics 2013, 29,
3073. (b) Aurélien, D. G.; Matthias, G.; Antoine, W.; Olivier, D.;
Zoete, M. V. Nucleic Acids Res. 2014, 42, 32.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–J