Synthesis of arylated and aminated naphthalenes and their synthetic applications for aza-heterocycles

Article abstract of DOI:10.1016/j.tet.2016.08.044

We have developed a new, metal free methodology for the synthesis of 3,4-diamino-2-methylsulfanyl-naphthalene-1-carbonitrile by reaction of 2-(1-cyano-2,2-bis(methylthio)vinyl)benzonitrile and nitromethane under basic conditions followed by reduction of n

Full text of DOI:10.1016/j.tet.2016.08.044

Tetrahedron 72 (2016) 6436e6443
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Synthesis of arylated and aminated naphthalenes and their
synthetic applications for aza-heterocycles
Surjeet Singh a, Ranjay Shaw a, Shallya, Sandeep Chaudhary b, Abhinav Kumar c,
,
Ramendra Pratap a
*
a Department of Chemistry, University of Delhi, North Campus, Delhi, 110007, India
b Department of Chemistry, MNIT, Jaipur, Rajasthan, 302017, India
c Department of Chemistry, University of Lucknow, Lucknow, Uttar Pradesh, 226007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 June 2016
Received in revised form 4 August 2016
Accepted 15 August 2016
Available online 16 August 2016
We have developed a new, metal free methodology for the synthesis of 3,4-diamino-2-methylsulfanyl-
naphthalene-1-carbonitrile by reaction of 2-(1-cyano-2,2-bis(methylthio)vinyl)benzonitrile and nitro-
methane under basic conditions followed by reduction of nitro group. We explored the synthetic po-
tential of 3,4-diamino-2-(methylthio)-1-naphthonitrile for the construction of different class of highly
functionalized fused polycyclic N-heterocycles, such as 3H-naphtho[1,2-d]imidazoles, benzo[f]quinoxa-
lines and 3H-naphtho[1,2-d][1,2,3]triazoles. 2-(1-Cyano-2,2-bis(methylthio)vinyl)benzonitrile also pro-
vides arylated naphthalenes and carbazole depending on use of functionalized 4-nitrotoluenes as
a carbanion source. The structure of some of the compounds was confirmed by single crystal X-ray
technique.
Keywords:
Naphthalene
Aza-heterocycles
2-Cyanomethyl benzonitrile
Ketenedithioacetal
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
heterocyclic compounds. 1,2-Diaminoarenes are very important
precursor for construction of various N-heterocycles by reaction
Ketene dithioacetals are versatile intermediates used for the
construction of large number of aromatic and heteroaromatic
skeletons. These molecules undergo addition, elimination, addi-
tion-elimination, and substitution reactions.1 Their synthetic utility
has been explored to construct various aromatic, heteroaromatic,
and nonaromatic ring systems of pharmaceutical and medicinal
importance.2 Recently, ketene dithioacetals are used for the syn-
thesis of functionalized 1-amino-2-aroyl/acetylnaphthalenes,3
partially reduced coumarins,4 2H-pyran-2-ones,4 various hetero-
cyclic compounds,4 and fluorescent molecules.5
It is well known that heterocyclic compounds exhibit broad
spectrum of medicinal and pharmaceutical applications.6 Amongst,
various heterocycles, nitrogen containing molecules are most
widely present in nature. Nitrogen heterocycles are present as
whole or substructures in various medicinally important com-
pounds, such as antiproliferative,7 antihistamines,8 antimalarial,9
antiviral,10 antithrombopoietic,11 and anti-inflammatory agents.12
Heterocyclic compounds are also present in dyes13 and act as key
intermediates for the synthesis of organic semiconductors.14 Vari-
ous approaches have been established for the synthesis of
with ketones and aldehydes.15 Recently, quinoxaline has been
synthesized by using 1,2-phenylenediamine as a precursor under
gallium(III) triflate-catalyzed conditions.16 In another approach
a-
hydroxy ketones are converted to quinoxalines via metal-catalyzed
aerobic oxidation using 2 mol % of Pd(OAc)2 or RuCl2(PPh3)3-TEMPO
as catalytic system.17 Vliet et al. have reported the one pot synthesis
of benzimidazoles by microwave irradiation.18 Various bicyclic 2H-
benzimidazoles have been also synthesized by reaction of various
aromatic and heteroaromatic 2-nitroamines, formic acid using iron
powder.19 Some other N-heterocycles such as carbazoles were
synthesized by intramolecular cross coupling reaction.20
Substituted biaryls and triazoles by 1,3-dipolar cycloaddition of
alkynes and azides.21 Apart from 1,2-diaminoarenes, [1,10-bi-
phenyl]-2-amines are also very interesting skeleton. They are
present as whole or substructure in various dyes and pigments.22
From literature it is clear that 1,2-diaminoarenes and [1,10-biaryl]-
2-amines are very interesting precursor used as key intermediate
for generating molecular diversity. These molecules have also been
used for the formation of various palladium (II) complexes,23 cyclic
urea,24 and quinones.25 All these applications gave us impetus to
establish a new protocol for the synthesis of highly functionalized
[1,10-biaryl]-2-amines and o-diaminonaphthalenes and use them
for synthesis of various N-heterocycles.
* Corresponding author. Fax: þ91 27666646; e-mail address: ramendrapratap@
gmail.com (R. Pratap).
http://dx.doi.org/10.1016/j.tet.2016.08.044
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

S. Singh et al. / Tetrahedron 72 (2016) 6436e6443
6437
2. Result and discussion
2,2-bis(methylthio)vinyl)benzonitrile (1) and nitromethane (2) was
performed under basic conditions. An accurate screening of various
base solvent combinations revealed that Et3N/DMSO and NaH/THF
combinations were ineffective. Then, we screened sodium hydride,
sodium hydroxide, potassium hydroxide, and sodamide as bases in
DMF and DMSO as solvents. Under these conditions compound 3
was isolated in 50e71%. Sodium hydride in DMSO gave rise to 4-
amino-2-methylsulfanyl-3-nitro-napthalene-1-carbonitrile (3) in
71% yield. Then, we performed the reduction26 of isolated com-
pound 3 using SnCl2$2H2O in EtOH at 100 ꢀC to afford 3,4-diamino-
2-methylsulfanyl-naphthalene-1-carbonitrile (4) in excellent yield.
3,4-Diaminonaphthalene 4 acts as key intermediate for the syn-
thesis of various heterocyclic compound as reported in Scheme 3.
We used various diketones as reagents for the synthesis of fused
quinoxalines 5aeb and tetrahydrobenzo[a]phenazine 6. We syn-
thesized compounds 5aeb and 6 by reaction of 4 with, respectively,
ethane-1,2-dione, diphenylethanone, and cyclohexandione in EtOH
at 100 ꢀC. In further exploration, 1-methyl-4-(methylthio)-2-aryl-
1H-naphtho[1,2-d]imidazole-5-carbonitriles (8aeg) were synthe-
sized in a two steps procedure. Initially, using a literature ap-
Herein, we wish to report the synthesis of various poly-
functionalized arylated and aminated naphthalenes from 2-(1-
cyano-2,2-bis(methylthio)vinyl)benzonitrile (1) and their use for
construction of different class of aza-heterocycles. Compound 1 is
a known compound and was synthesized by reaction of 2-
cyanomethyl benzonitrile, carbon disulphide, and methyl iodide
under basic conditions in THF (Scheme 1).3a Starting from 1 func-
tionalized o-diaminonaphthalene 4 was synthesized in a two steps
procedure, Scheme 2. In the first step, the reaction of 2-(1-cyano-
Scheme 1. Synthesis of 2-(1-cyano-2,2-bis(methylsulfanyl-vinyl)benzonitrile 1.
proach,27 by reaction of
4
with various functionalized
benzaldehydes, 4-(methylthio)-2-aryl-1H-naphtho[1,2-d]imidaz-
ole-5-carbonitriles were prepared. However, due to low solubility,
it was difficult to obtain good NMR spectra for these compounds.
Thus, to enhance their solubility, these compounds were methyl-
ated by using methyl iodide in DMF and cesium carbonate to afford
1-methyl-4-(methylthio)-2-aryl-1H-naphtho[1,2-d]imidazole-5-
carbonitriles (8aeg). Finally, we have further explored the syn-
thetic utility of 4 for the synthesis of fused triazole 7. 4-(Methyl-
thio)-1H-naphtho[1,2-d][1,2,3]triazole-5-carbonitrile
7
was
synthesized in 70% yield by reaction of 4 with NaNO2 in acetic acid
at 100 ꢀC.
Then, we further explored the synthetic potential of 2-(1-
cyano-2,2-bis(methylsulfanyl-vinyl)benzonitrile 1 using function-
alized 4-nitrotoluenes 9 as a source of nucleophiles for the syn-
thesis of arylated naphthalenes 10 using a (5þ1) annulation
Scheme 2. Synthesis of 4-amino-2-methylsulfanyl-3-nitro-napthalene-1-carbonitrile
3 and 3,4-diamino-2-methylsulfanyl-naphthalene-1-carbonitrile 4.
Scheme 3. Synthesis of various fused N-heterocycles (5e8).

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S. Singh et al. / Tetrahedron 72 (2016) 6436e6443
approach, Table 1 and Scheme 4. Initially using 1 and 2-bromo-4-
nitrotoluene 9a as model compounds, we screened various base
and solvent combinations for the synthesis of 10a at various tem-
peratures. We started our screening using sodium hydride as a base
and 9c the corresponding 4-amino-2-(methylthio)-3-aryl-1-
naphthonitriles 10bec were obtained in moderate yields. In-
terestingly, the use of 2-fluoro-1-methyl-4-nitrobenzene 9d pro-
vided 5-(methylthio)-9-nitro-11Hbenzo[a]carbazole-6-carbonitrile
(11) in lieu of the expected 4-amino-3-(2-fluoro-4-nitrophenyl)-2-
(methylthio)-1-naphthonitrile. This result is probably related to
a concurrent intramolecular cyclization involving NH2 group gen-
erated in situ and carbon containing fluoro group. We have also tried
2-methyl-5-nitrobenzonitrile as a nucleophile source, however only
a mixture of unidentified compounds was obtained.
Mechanistically, formation of product 4-amino-2-(methylthio)-
3-nitro-1-naphthonitrile (3) and 4-amino-2-(methylthio)-3-aryl-1-
naphthonitriles 10aec involves 5Cþ1C annulation sequence. From
structural investigation of 2-(1-cyano-2,2-bis(methylsulfanyl-vi-
nyl)benzonitrile, it is clear that C2 is more electrophilic due to
presence of nitrile and benzonitrile groups at position 1. Initially,
the carbanion generated in situ perform Michael addition on C2 of
2-(1-cyano-2,2-bis(methylsulfanylvinyl)benzonitrile followed by
loss of methanthiol and formation of intermediates A or A0. These
intermediates in presence of excess of base generate an allylic
carbanion able to attack nucleophilically the nitrile group to afford
intermediate B. Intermediate B by tautomerization finally affords
the desired product 3 or 10 (see Scheme 5).
Table 1
Optimization of reaction conditionsa,c
CN
MeS
SMe
Br
CH3
SMe
Br
Base/solvent
temp.
CN
CN
NH2
NO2
1
NO2
9a
10a
Entry
Base
Solvent
DMF
DMSO
DMSO
DMF
DMSO
DMF
DMF
DMSO
DMSO
DMF
DMSO
DMF
Time (h)
Yieldb,c (%)
1
2
3
4
5
6
7
8
NaH
NaH
5
5
5
5
5
5
5
5
2
2
2
2
2
2
Complex mixtureb
Complex mixture
Complex mixture
Complex mixture
Complex mixture
Complex mixtureb
Complex mixtureb
Complex mixture
Complex mixtureb
40
NaNH2
NaNH2
tBuOK
tBuOK
KOH
KOH
KOH
KOH
NaH
9d
10d
11d
12d
13d
14d
We have made several attempt to isolate intermediates A or A0
by shortening the reaction time or using substoichiometric
amounts of base. However, all these attempts failed probably be-
cause the proposed intermediate, once formed in the reaction
mixture, was immediately converted to the reaction product due to
presence of active methylene group.
Trace
35
Trace
30
NaH
NaNH2
DMF
DMF
tBuOK
a
Reactions were carried out by stirring 2-(1-cyno-2,2-bismethylsulfanyl-vinyl)-
benzonitrile (0.5 mmol), 2-Br-1-methyl-4-nitrobenzene (0.55 mmol), base
(1.0 mmol) in solvent (4.0 mL) at room temperature.
b
Incomplete reaction with left starting material.
c
RT¼25e35 ꢀC.
3. X-ray structural analysis
d
These reactions are carried out at 90 ꢀC. Bold faced line shows optimized re-
action condition.
The molecular views (ORTEP) for the both the compounds 5a and
10a with atom numbering scheme are presented in Figs. 1 and 2.28
In the case of 5a, the compound crystallizes in the triclinic
CH3
R
CH3
F
CN
MeS
SMe
CN
SMe
NC
NO2
9a-c
SMe
R
NO2
9d
NO2
KOH/DMF
90 oC
KOH/DMF
90 oC
N
H
11
CN
NH2
10
NO2
1
35 %
10a R = Br 40%
10b R= H 43 %
10c R = Cl 41%
Scheme 4. Synthesis of 4-amino-2-(methylthio)-3-aryl-1-naphthonitrile and 5-(methylthio)-9-nitro-11H-benzo[a]carbazole-6-carbonitriles.
in DMSO at room temperature. The reaction was carried out for 5 h
and formation of a complex mixture observed (Table 1, entry 1).
We also tried sodamide, potassium tert-butoxide, and potassium
hydroxide in DMF and DMSO at room temperature and complex
mixture were obtained within variable amount of starting mate-
rials (entries 2e9). The screening was then continued at higher
temperature (90 ꢀC). Trace amounts of the desired compound 10a
were obtained with NaH in DMSO and with NaNH2 in DMF (entries
11 and 13) while using DMF as reaction medium and KOH, NaH,
and BuOK as basic compound 10a was obtained in yields ranging
from 30 to 40% (entries 10, 12 and 14).
We then used the optimized reaction conditions reported inTable
1 entry 10 to synthesize some derivatives of arylated naphthalenes,
Scheme 4. We used 4-nitrotoluene (9b), 2-chloro-4-nitrotoluene (9c)
2-fluoro-4-nitrotoluene (9d) and as a carbanion source. In case of 9b
system having two molecules in the unit cell. The three fused rings
are essentially planar with small dihedral angle of 2.58ꢀ between
the pyrazine located at one end and phenyl ring at the other
terminus.
The dihedral angle between the central ring and the pyrazine
ring is 0.94ꢀ. The eSCH3 group is deviated by 0.259 A from the
ꢀ
plane of its aromatic ring while the cyano group is in plane with its
ꢀ
aromatic ring with slight deviation of 0.066 A.
In the case of 10a, there are four molecules in the monoclinic
unit cell. The napthalene ring is planar and is almost perpendicular
to 2-bromo-4-nitrophenyl ring. The dihedral angle between the
naphthyl ring and 2-bromo-4-nitrophenyl ring is 89.32ꢀ. In com-
parison to 5a the eSCH3 group is in plane of the naphthyl ring and
t
ꢀ
deviated merely by 0.074 A, while the cyano group is deviated by of
ꢀ
0.171 A.

S. Singh et al. / Tetrahedron 72 (2016) 6436e6443
6439
EWG
SMe
CN EWG
CN
MeS
NC
SMe
MeS
NC
SMe
and/or
EWG
OH
CH3
EWG
SMe
N
N
NC
EWG= -NO2, p-NO2;C6H4
NC
A'
A
Base
CN
CN
CN
CN EWG
CHN EWG
SMe
H
SMe
SMe
SMe
N
EWG
SMe
N
EWG
EWG
N
NH
NH2
A
B
Product
A'
Scheme 5. Mechanistic approach for the synthesis of 4-amino-2-methylsulfanyl-3-nitro-napthalene-1-carbonitrile and 4-amino-2-(methylthio)-3-aryl-1-naphthonitriles.
Fig. 1. ORTEP view with atom numbering scheme of compounds 5a with displacement
ellipsoids at the 30% probability level.
Fig. 3. Supramolecular architecture in 5a formed by the assistance of weak
CeH/N^C interactions.
vinyl)benzonitrile as precursor. The synthesized compound 3,4-
diamino-2-methylsulfanyl-naphthalene-1-carbonitrile act as
versatile intermediate and further explored for the synthesis of
various heterocyclic compound such as fused quinoxalines, im-
idazoles and triazoles. Our methodology for the synthesis of 3,4-
Fig. 2. ORTEP view with atom numbering scheme of compounds 10a with displace-
ment ellipsoids at the 30% probability level.
diamino-2-methylsulfanyl-naphthalene-1-carbonitrile and 4-
amino-2-(methylthio)-3-aryl-1-naphthonitrile avoids use of any
catalyst, harsh reaction conditions and multistep. 3,4-Diamino-2-
methylsulfanyl-naphthalene-1-carbonitrile can be used as pre-
cursor for synthesis of large class of heterocycles and some of
which is explored here as representative examples. We have also
demonstrated the synthesis of 4-amino-2-(methylthio)-3-aryl-1-
naphthonitriles, which can be used for synthesis of various bi-
ologically potent molecules especially carbazoles. In general,
arylation requires suitable precursor, metal catalyzed approach
and we have synthesized highly crowded arylated naphthalenes
under metal free condition. In conclusion, we can claim that 2-
(1-cyano-2,2-bis(methylsulfanyl-vinyl)benzonitrile is very ver-
satile precursor having vast synthetic potential.
The supramolecular aggregations in 5a are stabilized by a pair of
weak (Ar) CeH/N^C interactions (Fig. 3). The cyano group forms
a pair of intermolecular interaction with aromatic hydrogen atoms
ꢀ
ꢀ
one from the pyrazine CeH2/N3 (2.731 A; 126.60 ; symm. op. x,
ꢁ1þy, ꢁ1þz) and another belonging to the naphthyl ring
ꢀ
ꢀ
CeH10/N3 (2.653 A; 169.85 ; symm. op. x, ꢁ1þy, z). On the basis
of the interaction distance and angle parameters it can be said that
the second interaction is stronger than that of the first one.
The one dimensional supramolecular aggregations in 10a are
stabilized by weak NeH/N^C interactions (Fig. 4). The
ꢀ
NeH/N^C interaction distance and angle are 2.38(4) A and
153.01(4) (symm. op. ꢁ1/2þx, 3/2ꢁy,ꢁ1/2þz).
4. Conclusions
5. Experimental
5.1. General
In summary, we have developed a new simple and efficient
route for the synthesis of 3,4-diamino-2-methylsulfanyl-naph-
thalene-1-carbonitrile and 4-amino-2-(methylthio)-3-aryl-1-
naphthonitrile by using 2-(1-cyano-2,2-bis(methylsulfanyl-
Commercially available reagents from Sigma aldrich and Alfa
aesar were used without further purification. 1H and 13C NMR

6440
S. Singh et al. / Tetrahedron 72 (2016) 6436e6443
Fig. 4. One dimensional chain motif in 10a formed by the assistance of weak NeH/N^C interactions.
spectra were recorded on a 400 MHz NMR and 100 MHz NMR
spectrometer and CDCl3 and DMSO-d6 was used as solvent.
Chemical shifts for all the compounds are reported in parts per
(40% ethylacetate-hexane) 0.25, mp: 123e124 ꢀC; IR (KBr): 3368,
2932, 2203 cmꢁ1 1H NMR (400 MHZ, CDCl3):
2.47 (s, 3H,
;
d
eSeCH3), 4.35 (br s, 4H, eNH2) 7.41e7.53 (m, 2H, ArH), 7.64e7.71
million shift as
d-value from CDCl3 (d
7.24 ppm for 1H and
(m, 1H, ArH), 8.07e8.13 (m, 1H, ArH); 13C NMR (100 MHZ, CDCl3):
77.00 ppm for 13C NMR) as an internal standard. Signal patterns are
mentioned as s, singlet; d, doublet; dd, double doublet; t, triplet; m,
multiplet; bs, broad singlet and bm, broad multiplet. Coupling
constants (J) for protons are given in hertz (Hz). Infrared (IR) spectra
was recorded on a PerkineElmer AX-1 spectrophotometer and re-
ported in wave number (cmꢁ1). HRMS reported are showing the
peak for MHþ. Synthesis of 2-(1-cyno-2,2-bismethylsulfanyl-vinyl)-
benzonitrile was performed by reported procedure.3 Intensity data
for both the compounds were collected at 298(2) K on an Agilent
d
18.9, 105.4, 117.9, 119.9, 122.3, 125.9, 126.0, 126.6, 129.6, 130.1,
130.2, 133.5; HRMS (ESI): (MHþ), found 230.0747, requires for
12H11N3S, 230.0746.
C
5.1.3. General procedure synthesis of functionalized benzo[f]qui-
noxaline-6-carbonitriles 5a, 5b and 6. A mixture of 3,4-diamino-2-
(methylthio)-1-naphthonitrile 4 (0.5 mmol, 0.114 g) and 1,2-
dicarbonyl compound (0.55 mmol) in EtOH (5.0 mL) was refluxed
at 100 ꢀC for 6e7 h. After completion of reaction, desired product
was precipitated in ethanol. Cooled the reaction mixture and filtered
the obtained precipitate, dried and recrystallized with ethanol.
Xcalibur diffractometer using graphite monochromated Mo-K
a
ꢀ
radiation
l¼0.71073 A. Unit cell determination, data collection, and
data reduction were performed with CrysAlisPro.29 The structure
was solved by direct methods (SIR97)30 and refined by a full-matrix
least-squares procedure based on F2.31 All non-hydrogen atoms
were refined anisotropically; hydrogen atoms were located at cal-
culated positions and refined using a riding model. All hetero hy-
drogen atoms have been located in the difference Fourier map and
were refined with bond lengths restraints.
5.1.4. 5-(Methylthio)benzo[f]quinoxaline-6-carbonitrile 5a. A mix-
ture of 3,4-diamino-2-(methylthio)-1-naphthonitrile 4 (0.5 mmol,
0.114 g) and ethane-1,2-dione (0.55 mmol, 0.025 mL) in EtOH
(5.0 mL) was refluxed at 100 ꢀC for 6e7 h. After completion, cooled
the reaction mixture and filtered the obtained precipitate, and
recrystallized with ethanol to afford the 66% (0.082 g) of light
yellow solid. Rf (10% ethylacetate-hexane) 0.42, mp: 175e177 ꢀC; IR
5.1.1. Synthesis of 4-amino-2-(methylthio)-3-nitro-1-naphthonitrile
3. A mixture of 2-(1-cyno-2,2-bismethylsulfanyl-vinyl)-benzoni-
trile 1 (0.5 mmol, 0.123 g), nitromethane 2 (0.55 mmol, 0.029 mL)
and powdered NaH (1 mmol, 0.024 g) in dry DMSO (4.0 mL) was
stirred at room temperature for 1 h under. After completion of re-
action, the mixture was poured onto ice-water with constant stir-
ring followed by neutralization with 10% HCl. The obtained
precipitate was filtered, washed with cold water and dried over
sodium sulfate. The crude product was purified by silica gel column
chromatography using 20% ethylacetate in hexane as an eluent to
afford 71% (0.083 g) of the compound as brown solid. Rf (30%
ethylacetate-hexane) 0.29, mp: 217e219 ꢀC; IR (KBr): 3357, 2927,
(KBr): 2923, 2218 cmꢁ1 1H NMR (400 MHZ, CDCl3):
; d 2.86 (s, 3H,
eSeCH3), 7.80e7.91 (m, 2H, ArH), 8.29e8.35 (m, 1H, ArH),
9.00e9.08 (m, 2H, ArH), 9.19e9.24 (m, 1H, ArH); 13C NMR (100
MHZ, CDCl3):
d 19.6, 115.7, 116.8, 124.9, 125.4, 128.8, 130.2, 130.7,
130.9, 140.7, 142.6, 144.0, 144.5, 145.4; HRMS (ESI): (MHþ); found
252.0590, requires for C14H9N3S, 252.0590.
5.1.5. 5-(Methylthio)-2,3-diphenylbenzo[f]quinoxaline-6-carbonitrile
5b. A mixture of 3,4-diamino-2-(methylthio)-1-naphthonitrile 4
(0.5 mmol, 0.114 g) and benzil (0.55 mmol, 0.116 g) in EtOH (5.0 mL)
was refluxed at 100 ꢀC for 6e7 h. After completion, cooled the re-
action mixture and filtered the obtained precipitate, dried and
recrystallized with ethanol to get 70% (0.143 g) of light yellow solid.
Rf (10% ethylacetate-hexane) 0.40, mp: 209e211 ꢀC; IR (KBr): 2928,
2216, cmꢁ1; 1H NMR (400 MHZ, CDCl3):
d 2.67 (s, 3H, eSeCH3), 6.32
(s. 2H, eNH2), 7.65 (t, J¼7.7 Hz, 1H, ArH), 7.79 (t, J¼7.7 Hz, 1H, ArH),
7.90 (d, J¼8.8 Hz,1H, ArH), 8.19 (d, J¼8.8 Hz,1H, ArH); 13C NMR (100
2215 cmꢁ1 1H NMR (400 MHZ, CDCl3):
; d 2.96 (s, 3H, eSeCH3),
MHZ, DMSO):
d
20.0, 100,8, 116.7, 122.1, 124.5, 124.8, 127.5, 131.6,
7.30e7.46 (m, 6H, ArH) 7.60e7.72 (m, 4H, ArH), 7.76e7.88 (m, 2H,
132.9, 133.1, 135.6, 142.5; HRMS (ESI): (MHþ), found 260.0488, re-
quires C12H9N3O2S, 260.0488.
ArH), 8.30 (d, J¼8.0 Hz, 1H, ArH), 9.26 (d, J¼8.0 Hz, 1H, ArH); 13C
NMR (100 MHZ, CDCl3): d 19.7, 115.2, 116.1, 125.1, 125.4, 128.3, 128.4,
128.5, 129.3, 129.5, 130.0, 130.1, 130.4, 131.1, 138.2, 138.3, 138.4,
139.9, 141.1, 152.5, 153.3; HRMS (ESI): (MHþ); found 404.1216, re-
quires for C26H17N3S, 404.1216.
5.1.2. Synthesis of 3,4-diamino-2-(methylthio)-1-naphthonitrile 4. A
solution of 4-amino-2-(methylthio)-3-nitro-1-naphthonitrile
3
(0.5 mmol, 0.129 g) in EtOH (5.0 mL) in presence of SnCl2$2H2O
(2.5 mmol, 0.562 g) was refluxed at 90 ꢀC for 1 h. Completion of
reaction was monitored by TLC. Excess EtOH was removed under
reduced pressure. Crude mixture was poured onto crushed ice and
pH was made slightly basic by addition of 10% aqueous sodium
bicarbonate. Filter the obtained precipitated and filtrate was
extracted with ethyl acetate (30 mLꢂ3). Organic layer was dried
over sodium sulfate and crude product was purified by silica gel
column chromatography using 35% ethyl acetate in hexane as an
eluent to afford 90% (0.103 g) of desired product as brown solid. Rf
5.1.6. 6-(Methylthio)-8,9,10,11-tetrahydrobenzo[a]phenazine-5-
carbonitrile 6. A mixture of 3,4-diamino-2-(methylthio)-1-
naphthonitrile 4 (0.5 mmol, 0.114 g) and cyclohexane-1,2-dione
(0.55 mmol, 0.062 g) in EtOH (5.0 mL) was refluxed at 100 ꢀC for
6e7 h. After completion, cooled the reaction mixture and filtered
the obtained precipitate, dried and recrystallized with ethanol to
afford 65% (0.099 g) of yellow solid; Rf (20% ethylacetate-hexane)
0.72, mp: 203e205 ꢀC; IR (KBr): 2951, 2855, 2219 cmꢁ1
;
1H NMR
(400 MHZ, CDCl3): 2.02e2.10 (m, 4H, eCH2e), 2.86 (s, 3H,
d

S. Singh et al. / Tetrahedron 72 (2016) 6436e6443
6441
eSeCH3), 3.19e3.26 (m, 4H, eCH2e), 7.71e7.82 (m, 2H, ArH),
8.23e8.27 (m, 1H, ArH), 9.11e9.16 (m, 1H, ArH); 13C NMR (100 MHZ,
6e8 h. Cooled the reaction mixture and filtered the obtained
product and proceed for methylation by stirring the crude, MeI
(0.55 mmol, 0.035 mL) and Cs2CO3 in THF at 0e5 ꢀC for 1 h. After
completion of reaction, excess of THF was removed under vacuum.
The mixture was poured onto ice-water with constant stirring
followed by neutralization with 10% HCl. The obtained precipitate
was filtered, dried and purified by silica gel column chromatogra-
phy using 20% ethylacetate in hexane as an eluent to obtain 65%
(0.111 g) of orange solid. Rf (25% ethylacetate-hexane) 0.30, mp:
214e216 ꢀC; IR (KBr): 2919, 2203 cmꢁ1; 1H NMR (400 MHZ, CDCl3):
CDCl3):
d 19.8, 22.6, 22.6, 32.9, 33.1, 114.6, 116.1, 124.6, 125.2, 128.2,
129.8, 130.1, 130.6, 138.5, 140.0, 143.7, 154.2, 155.3; HRMS (ESI):
(MHþ); found 306.1058, requires for C18H15N3S, 306.1059.
5.1.7. Synthesis of 4-(methylthio)-1H-naphtho[1,2-d][1,2,3]triazole-
5-carbonitrile 7. A mixture of 3,4-diamino-2-(methylthio)-1-
naphthonitrile 4 (0.5 mmol, 0.114 gm) and NaNO2 (0.55 mmol) in
CH3COOH (5.0 mL) was heated at 100 ꢀC for 2 h. After completion,
excess of CH3COOH was removed under vacuum. Crude material
was neutralized with 10% aqueous solution of sodium bicarbonate.
Precipitate obtained was filtered, dried and purified by silica gel
column chromatography using 30% ethylacetate in hexane as an
eluent to afford 70% (0.084 g) of brown solid. Rf (30% ethylacetate-
hexane) 0.22, mp: 212e214 ꢀC; IR (KBr): 3448, 2925, 2221 cmꢁ1; 1H
d
2.45 (s, 3H, eCH3), 2.97 (s, 3H, eSeCH3), 4.26 (s, 3H, eNeCH3),
7.35 (d, J¼7.9 Hz, 2H, ArH) 7.53e7.70 (m, 4H, ArH), 8.32e8.37 (m,
1H, ArH), 8.39e8.45 (m, 1H, ArH); 13C NMR (100 MHZ, CDCl3):
d
18.6, 21.4, 36.2, 106.5, 117.4, 120.5, 121.5, 126.3, 126.4, 126.6, 126.7,
129.4, 129.8, 130.6, 132.4, 137.6, 139.8, 140.4, 154.8; HRMS (ESI):
(MHþ); found 344.1220, requires for C21H17N3S, 344.1216.
NMR (400 MHZ, DMSO-d6):
d 3.08 (s, 3H, eSeCH3), 3.15 (s, 1H,
eNHe), 7.78e7.90 (m, 2H, ArH), 8.10e8.14 (m, 1H, ArH), 8.46 (d,
5.1.11. 2-(4-Bromo-phenyl)-1-methyl-4-methylsulfanyl-1H-naptho
[1,2-d]imidazole-5-carbonitrile 8c. A mixture of 3,4-diamino-2-
(methylthio)-1-naphthonitrile 4 (0.5 mmol, 0.114 g) and 4-
J¼7.3 Hz, 1H, ArH); 13C NMR (100 MHz, DMSO-d6):
d
17.6, 116.0,
123.3,124.9,128.2,129.5,130.1; HRMS (ESI): (MHþ) found 241.0540,
requires for C12H8N4S, 241.0542.
bromobenzaldehyde (0.55 mmol, 0.102 g) in EtOH (5.0 mL) was
refluxed at 100 ꢀC for 6e8 h. Obtained precipitate was filtered and
dried under vacuum. Further, a mixture of crude, MeI (0.55 mmol,
0.035 mL) and Cs2CO3 in THF was stirred at 0e5 ꢀC for 1 h. After
completion of reaction, excess of THF was removed under vacuum.
The mixture was poured onto ice-water with constant stirring
followed by neutralization with 10% HCl. The obtained precipitate
was filtered, dried and purified by silica gel column chromatogra-
phy using 20% ethylacetate in hexane as an eluent and isolated 61%
(0.124 g) of orange solid. Rf (30% ethylacetate-hexane) 0.38, mp:
267e269 ꢀC; IR (KBr): 2922, 2203 cmꢁ1; 1H NMR (400 MHZ, CDCl3):
5.1.8. General procedure for the synthesis of 1-methyl-4-(methyl-
thio)-2-aryl-1H-naptho[1,2-d]imidazole-5-carbonitrile
(8aeg). A
mixture of 3,4-diamino-2-(methylthio)-1-naphthonitrile
4
(0.5 mmol, 0.114 g) and substituted benzaldehyde (0.55 mmol) in
EtOH (5.0 mL) was refluxed at 100 ꢀC for 6e8 h. After completion,
obtained precipitate was filtered and dried under vacuum. Due to
lack of solubility of 4-(methylthio)-2-aryl-1H-naphtho[1,2-d]imid-
azole-5-carbonitrile characterization was very difficult. In further
step crude product obtained was directly methylated. We have
stirred a mixture of 4-(methylthio)-2-aryl-1H-naphtho[1,2-d]im-
idazole-5-carbonitrile (0.5 mmol) and MeI (0.55 mmol) and Cs2CO3
in THF at 0e5 ꢀC for 1 h. After completion of reaction, excess of THF
was removed under vacuum. The mixture was poured onto ice-
water with constant stirring followed by neutralization with 10%
HCl. The obtained precipitate was filtered, dried and purified by
silica gel column chromatography using 20% ethylacetate in hexane
as an eluent.
d
2.96 (s, 3H, eSeCH3), 4.28 (s, 3H, eNeCH3), 7.63e7.73 (m, 6H,
AreH), 8.36e8.46 (m, 2H, AreH); HRMS (ESI): (MHþ); found
408.0162, requires for C20H14BrN3S, 408.0165.
5.1.12. 2-(4-Chlorophenyl)-1-methyl-4-(methylthio)-1H-naphtho
[1,2-d]imidazole-5-carbonitrile 8d. A mixture of 3,4-diamino-2-
(methylthio)-1-naphthonitrile
4 (0.5 mmol, 0.114 g) and 4-
chlorobenzaldehyde (0.55 mmol, 0.078 g) in EtOH (5.0 mL) was
refluxed at 100 ꢀC for 6e8 h. Obtained precipitate was filtered and
dried under vacuum. Further, a mixture crude, MeI (0.55 mmol,
0.035 mL) and Cs2CO3 in THF was stirred at 0e5 ꢀC for 1 h. Usual
work-up purification by silica gel column chromatography using
20% ethylacetate in hexane as an eluent provides 60% (0.108 g) of
yellow solid; Rf (30% ethylacetate-hexane) 0.42, mp: 185e187 ꢀC; IR
5.1.9. 1-Methyl-4-(methylthio)-2-phenyl-1H-naptho[1,2-d]imidaz-
ole-5-carbonitrile 8a. A mixture of 3,4-diamino-2-(methylthio)-1-
naphthonitrile
4
(0.5 mmol, 0.114 g) and benzaldehyde
(0.55 mmol, 0.056 mL) in EtOH (5.0 mL) was refluxed at 100 ꢀC for
6e8 h. Obtained precipitate was filtered and dried under vacuum
and crude was methylated by stirring with MeI (0.55 mmol,
0.035 mL) and Cs2CO3 in THF at 0e5 ꢀC for 1 h. After completion of
reaction, excess of THF was removed under vacuum. The mixture
was poured onto ice-water with constant stirring followed by
neutralization with 10% HCl. The obtained precipitate was filtered,
dried and purified by silica gel column chromatography using 20%
ethylacetate in hexane as an eluent and isolated 63% (0.103 g)
golden color solid. Rf (25% ethylacetate-hexane) 0.32, mp:
182e184 ꢀC; IR (KBr): 2919, 2204 cmꢁ1; 1H NMR (400 MHZ, CDCl3):
(KBr): 2918, 2211 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d 2.65 (s, 3H,
eSeCH3), 4.30 (s, 3H, eNeCH3), 7.52e7.57 (m, 2H, ArH) 7.61e7.75
(m, 4H, ArH), 8.25e8.29 (dd, J¼1.4 Hz, 1H, ArH), 8.64e8.71 (m, 1H,
ArH); 13C NMR (100 MHZ, CDCl3):
d 21.3, 35.2, 113.1, 117.2, 122.6,
125.5,126.3,127.3, 127.6,127.9,128.1,129.2,130.2,131.2,131.4,136.6,
142.2, 155.3; HRMS (ESI): (MHþ); found 364.0676, requires for
C20H14ClN3S, 364.0670.
5.1.13. 2-(4-Fluorophenyl)-1-methyl-4-(methylthio)-1H-naphtho
d
2.96 (s, 3H, eSeCH3), 4.27 (s, 3H, eNeCH3), 7.52e7.65 (m, 5H,
ArH), 7.73e7.79 (m, 2H, ArH), 8.28e8.33 (m, 1H, ArH), 8.39e8.44
(m, 1H, ArH); 13C NMR (100 MHZ, CDCl3):
18.6, 36.1, 106.6, 117.4,
[1,2-d]imidazole-5-carbonitrile 8e. A mixture of 3,4-diamino-2-
(methylthio)-1-naphthonitrile
4 (0.5 mmol, 0.114 g) and 4-
d
fluorobenzaldehyde (0.55 mmol, 0.059 mL) in EtOH (5.0 mL) was
refluxed at 100 ꢀC for 6e8 h. Obtained precipitate was filtered and
dried under vacuum. In further step we have stirred the crude
mixture, MeI (0.55 mmol, 0.035 mL) and Cs2CO3 in THF at 0e5 ꢀC
for 1 h. Usual work-up and purification over silica gel column
chromatography using 20% ethylacetate in hexane as an eluent
provides 58% (0.100 g) of yellow solid. Rf (30% ethylacetate-
120.5, 121.4, 126.5, 126.5, 126.8, 128.8, 129.2, 129.9, 130.1, 130.6,
132.4, 137.7, 139.7, 154.6; HRMS (ESI): (MHþ); found 330.1065, re-
quires for C20H15N3S, 330.1059.
5.1.10. 1-Methyl-4-(methylthio)-2-(p-tolyl)-1H-naphtho[1,2-d]imid-
azole-5-carbonitrile 8b. A mixture of 3,4-diamino-2-(methylthio)-
1-naphthonitrile 4 (0.5 mmol, 0.114 g) and 4-methylbenzaldehyde
(0.55 mmol, 0.065 mL) in EtOH (5.0 mL) was refluxed at 100 ꢀC for
hexane) 0.40, mp: 184e186 ꢀC; IR (KBr): 2921, 2207 cmꢁ1
;
1H
NMR (400 MHz, CDCl3): 2.67 (s, 3H, eSeCH3), 4.31 (s, 3H,
d

6442
S. Singh et al. / Tetrahedron 72 (2016) 6436e6443
eNeCH3), 7.21e7.31 (m, 2H, ArH) 7.62e7.72 (m, 2H, ArH),
7.74e7.83 (m, 2H, ArH), 8.26e8.32 (m, 1H, ArH), 8.67e8.72 (m, 1H,
J¼2.2 Hz, 1H, ArH), 8.63 (d, J¼2.2 Hz, 1H, ArH); 13C NMR (100 MHZ,
CDCl3):
d 19.9, 104.6, 117.4, 121.4, 121.5, 123.1, 126.0, 126.4, 126.9,
ArH); 13C NMR (100 MHz, CDCl3):
d
21.3, 35.2, 112.2, 116.1(d,
128.5, 129.6, 133.2, 134.4, 141.6, 143.3, 144.6, 148.2; HRMS (ESI):
JCeF¼22.0 Hz), 117.3, 122.6, 125.6, 125.6, 126.3, 127.3, 127.6, 128.1,
130.2, 131.4, 132.0 (d, JCeF¼8.6 Hz), 142.3, 155.5, 163.8 (d,
JCeF¼248.2 Hz); HRMS (ESI): (MHþ); found 348.0976, requires for
(MHþ); found 413.9907, requires for C18H12BrN3O2S, 413.9906.
5.1.18. 4-Amino-2-(methylthio)-3-(4-nitrophenyl)-1-naphthonitrile
10b. A mixture of 2-(1-cyno-2,2-bismethylsulfanyl-vinyl)-benzo-
nitrile 1 (0.5 mmol, 0.123 g), 4-nitrotoluene (0.55 mmol, 0.076 g)
and powdered KOH (1 mmol, 0.056 g) in dry DMF (4.0 mL) was
stirred at 90 ꢀC for 2 h. Usual work-up and purification by silica gel
column chromatography using 20% ethyl acetate in hexane as an
eluent afforded 43% (0.072 g) of brown solid. Rf (20% ethylacetate-
hexane) 0.32. Mp: 282e284 ꢀC; IR (KBr): 2922, 2213 cmꢁ1; 1H NMR
C
20H14FN3S, 348.0965.
5.1.14. 1-Methyl-4-(methylthio)-2-(2-nitrophenyl)-1H-naptho[1,2-d]
imidazole-5-carbonitrile 8f. A mixture of 3,4-diamino-2-(methyl-
thio)-1-naphthonitrile
4
(0.5 mmol, 0.114 g) and 2-
nitrobenzaldehyde (0.55 mmol, 0.084 g) in EtOH (5.0 mL) was
refluxed at 100 ꢀC for 6e8 h. Obtained precipitate was filtered and
dried under vacuum. In further step, stirred the crude mixture,
(0.5 mmol, 0.181 g), MeI (0.55 mmol, 0.035 mL) and Cs2CO3 in THF
at 0e5 ꢀC for 1 h. Usual work-up and purification by silica gel col-
umn chromatography using 20% ethylacetate in hexane as an elu-
ent afforded 45% (0.084 g) of brown solid. Rf (30% ethylacetate-
(400 MHZ, DMSO):
7.53e7.63 (m, 3H, ArH) 7.71e7.78 (m,1H, ArH), 7.98 (d, J¼8.8 Hz,1H,
ArH), 8.32e8.42 (m, 3H, ArH); 13C NMR (100 MHZ, DMSO):
19.3,
d 2.24 (s, 3H, eSeCH3), 6.38 (s, 2H, eNH2),
d
99.8, 117.8, 120.6, 121.1, 123.7, 124.1, 124.3, 125.9, 129.5, 132.5, 133.7,
140.8, 144.4, 146.6, 147.0; HRMS (ESI): (MHþ); found 336.0800, re-
quires for C18H13N3O2S, 336.801.
hexane) 0.30, mp: 309e311 ꢀC; IR (KBr): 2919, 2203 cmꢁ1
NMR (400 MHZ, CDCl3): 2.86 (s, 3H, eSeCH3), 4.09 (s, 3H,
eNeCH3), 7.62e7.88 (m, 5H, ArH), 8.24e8.29 (dd, J¼1.5 Hz, 1H,
ArH), 8.35e8.45 (m, 2H, ArH); 13C NMR (100 MHZ, CDCl3):
18.7,
;
1H
d
5.1.19. 4-Amino-3-(2-chloro-4-nitrophenyl)-2-(methylthio)-1-
naphthonitrile 10c. A mixture of 2-(1-cyno-2,2-bismethylsulfanyl-
vinyl)-benzonitrile 1 (0.5 mmol, 0.123 g), 2-chloro-1-methyl-4-
nitrobenzene (0.55 mmol, 0.095 g) and powdered KOH (1 mmol,
0.056 g) in dry DMF (4.0 mL) was stirred at 90 ꢀC for 2 h. Usual
work-up and purification by silica gel column chromatography
using 20% ethyl acetate in hexane as an eluent provides 41%
(0.075 g) of brown solid. Rf (20% ethylacetate-hexane) 0.29, mp:
134e136 ꢀC; IR (KBr): 2916, 2207 cmꢁ1; 1H NMR (400 MHZ, DMSO):
d
35.1, 107.5, 117.2, 120.6, 121.5, 125.0, 125.3, 126.8, 126.9, 127.1, 130.9,
131.5, 131.7, 133.2, 133.7, 137.8, 139.8, 148.9, 150.1; HRMS (ESI):
(MHþ); found 375.0915, requires for C20H14N4O2S, 375.0910.
5.1.15. 1-Methyl-4-methylsulfanyl-2-(4-nitro-phenyl)-1H-naptho
[1,2-d]imidazole-5-carbonitrile 8g. A mixture of 3,4-diamino-2-
(methylthio)-1-naphthonitrile
4 (0.5 mmol, 0.114 g) and 4-
nitrobenzaldehyde (0.55 mmol, 0.084 g) in EtOH (5.0 mL) was
refluxed at 100 ꢀC for 6e8 h. Obtained precipitate was filtered and
dried under vacuum. In further step, stirred the crude, MeI
(0.55 mmol, 0.035 mL) and Cs2CO3 in THF at 0e5 ꢀC for 1 h. Usual
work-up and purification by silica gel column chromatography
using 20% ethylacetate in hexane as an eluent afforded 55%
(0.102 g) of brown solid. Rf (30% ethylacetate-hexane) 0.32, mp:
267e269 ꢀC; IR (KBr): 2925, 2210 cmꢁ1; 1H NMR (400 MHZ, CDCl3):
d
2.39 (s, 3H, eSeCH3), 4.43 (s, 2H, eNH2), 7.45 (d, J¼8.0 Hz, 1H,
ArH), 7.52e7.58 (m, 1H, ArH), 7.64e7.71 (m, 1H, ArH), 7.76 (d,
J¼8.0 Hz, 1H, ArH), 8.18e8.26 (m, 2H, ArH), 8.42 (d, J¼2.2 Hz, 1H,
ArH); 13C NMR (100 MHZ, DMSO):
d 19.9, 104.8, 117.3, 119.6, 121.4,
121.4, 122.5, 125.4, 126.1, 127.0, 129.6, 133.4, 134.4, 136.4, 141.6,
142.3, 143.5, 148.3; HRMS (ESI): (MHþ); found 370.0418, requires
for C18H12ClN3O2S, 370.0412.
d
2.69 (s, 3H, eSeCH3), 4.39 (s, 3H, eNeCH3), 7.67e7.77 (m, 2H,
5.1.20. Synthesis of 6-(methylthio)-9-nitro-11H-benzo[a]carbazole-
5-carbonitrile 11. A mixture of 2-(1-cyno-2,2-bismethylsulfanyl-
vinyl)-benzonitrile 2 (0.5 mmol, 0.123 g), 2-fluoro-1-methyl-4-
nitrobenzene (0.5 mmol, 0.085 g) and powdered KOH (1 mmol,
0.056 g) in dry DMF (4.0 mL) was stirred at 90 ꢀC for 2 h. After
completion of reaction, the mixture was poured onto ice-water
with constant stirring followed by neutralization with 10% HCl.
The obtained precipitate was filtered and dried. The crude
product was purified by silica gel column chromatography using
20% ethylacetate in hexane as an eluent and 35% (0.058 g) of
white solid was isolated; Rf (20% ethylacetate-hexane) 0.21, mp:
ArH), 8.02 (d, J¼8.8 Hz, 2H, ArH), 8.32 (d, J¼8.7 Hz,1H, ArH), 8.44 (d,
J¼8.0 Hz, 2H, ArH), 8.69e8.75 (m, 1H, ArH); HRMS (ESI): (MHþ);
found 375.0916, requires for C20H14N4O2S, 375.0910.
5.1.16. General procedure synthesis of 4-amino-2-(methylthio)-3-
aryl-1-naphthonitrile (10aec). A mixture of 2-(1-cyno-2,2-
bismethylsulfanyl-vinyl)-benzonitrile 1 (0.5 mmol, 0.123 g) and 2-
Br/Cl/H-1-methyl-4-nitrobenzene (0.55 mmol) and powdered
KOH (1 mmol, 0.056 g) in dry DMF (4.0 mL) was stirred at 90 ꢀC for
2 h. Reaction was monitored by TLC. After completion, reaction
mixture was poured onto ice-water with constant stirring followed
by neutralization with 10% HCl. The obtained precipitate was fil-
tered and dried. The crude product was purified by silica gel column
chromatography using 20% ethyl acetate in hexane as an eluent.
339e341 ꢀC; IR (KBr): 3335, 2925, 2205 cmꢁ1
;
1H NMR (400
MHZ, DMSO): 2.68 (s, 3H, eSeCH3), 7.86e7.93 (m, 2H, ArH),
d
8.17e8.24 (m, 2H, ArH), 8.46 (d, J¼2.2 Hz, 1H, ArH), 8.60e8.66
(m, 1H, ArH), 8.83 (d, J¼8.8 Hz, 1H, ArH), 13.4 (s, 1H, -NH-); 13C
NMR (100 MHz, DMSO):
d 19.9, 107.1, 107.7, 115.4, 116.4, 117.0,
5.1.17. 4-Amino-3-(2-bromo-4-nitrophenyl)-2-(methylthio)-1-
naphthonitrile 10a. A mixture of 2-(1-cyno-2,2-bismethylsulfanyl-
vinyl)-benzonitrile 1 (0.5 mmol, 0.123 g), 2-bromo-1-methyl-4-
nitrobenzene (0.55 mmol, 0.119 g) and powdered KOH (1 mmol,
0.056 g) in dry DMF (4.0 mL) was stirred at 90 ꢀC for 2 h. Usual
work-up and purification by silica gel column chromatography
using 20% ethyl acetate in hexane as an eluent provides 40%
(0.082 g) of brown solid. Rf (20% ethylacetate-hexane) 0.31, mp:
136e138 ꢀC; IR (KBr): 2917, 2209 cmꢁ1; 1H NMR (400 MHZ, CDCl3):
120.0, 122.6, 123.1, 125.2, 127.1, 127.9, 129.4, 131.2, 138.1, 138.3,
140.8, 144.4; HRMS (ESI): (MHþ); found 334.0649, requires for
C
18H11N3O2S, 334.0645.
Acknowledgements
R.P. thank Council of Scientific and Industrial Research (CSIR,
New Delhi) [Project No. 02(0080)/12/EMR-II], Department of Sci-
ence and Technology (DST, New Delhi) [Project No. SB/FT/CS-049/
2012 and DST-DU Purse grant] and University of Delhi, Delhi [R & D
Grant] for financial support. S.S. and R.S. thanks Council of Scientific
and Industrial Research (CSIR, New Delhi) and R.S. and S. thank
d
2.46 (s, 3H, eSeCH3), 4.47 (s, 2H, eNH2), 7.48 (d, J¼8.0 Hz, 1H,
ArH), 7.57e7.63 (m, 1H, ArH), 7.72 (t, J¼8.0 Hz, 1H, ArH), 7.81 (d,
J¼8.8 Hz, 1H, ArH), 8.25 (d, J¼8.8 Hz, 1H, ArH), 8.32e8.42 (dd,

S. Singh et al. / Tetrahedron 72 (2016) 6436e6443
6443
13. (a) Brock, E. D.; Lewis, D. M.; Yousaf, T. I.; Harper, H. H. (The Procter and Gamble
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Chem. 2002, 39, 303.
University Grants Commission (UGC, New Delhi) for research fel-
lowship. Authors thank USIC, Delhi University and instrumentation
facility.
14. (a) O’Brien, D.; Weaver, M. S.; Lidzey, D. G.; Bradley, D. D. C. Appl. Phys. Lett.
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Supplementary data
15. (a) Porter, A. E. A. In Comprehensive Heterocyclic Chemistry; Katritsky, A. R., Rees,
C. W., Eds.; Pergamon: Oxford, 1984; p 157; (b) Wagner, E. C.; Millett, W. H. Org.
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Supplementary data related to this article can be found, in the
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€
28. Crystal Data 5a (CCDC 1422163): C14H9N3S, M¼251.30, Triclinic, Pꢁ1, a¼7.
3493(13) A, b¼9.3049(19) A, c¼10.0874(19) A,
a
¼115.323(19)ꢀ
b
¼108.578(16)ꢀ,
ꢀ
ꢀ
ꢀ
ꢀ
3
g
¼91.193(16) , V¼581.0(2) A , Z¼2, Dcalcd¼1.436 mg mꢁ3, F(000)¼260, crystal
ꢀ
size 0.400ꢂ0.180ꢂ0.150 mm, reflections collected 4300, independent re-
flections 2442 [R(int)¼0.0148], Final indices [I>2 (I)] R1¼0.0368 wR2¼0.1009, R
s
indices (all data) R1¼0.0416, wR2¼0.1055, gof 1.059, Largest difference peak and
ꢀꢁ3
hole 0.211 and ꢁ0.207 e A .Crystal Data 10a (CCDC 1422164): C18H12BrN3O2S,
ꢀ
ꢀ
ꢀ
M¼414.28, Monoclinic, P 21/n, a¼10.8942(17) A, b¼11.515(3) A, c¼14.123(2) A,
3
ꢀ
b
¼90.653(15) , V¼1771.5(6) A , Z¼4, Dcalcd¼1.553 mg mꢁ3, F(000)¼832, crystal
ꢀ
size 0.230ꢂ0.200ꢂ0.180 mm, reflections collected 7469, independent re-
flections 3523 [R(int)¼0.0273], Final indices [I>2
indices (all data) R1¼0.1068, wR2¼0.1412, gof 1.030, Largest difference peak and
ꢀꢁ3
s(I)] R1¼0.0644 wR2¼0.1233, R
hole 0.616 and ꢁ0.402 e A
.
29. DENZO-SCALEPACK Otwinowski, Z.; Minor, W. Processing of X-ray diffraction
data collected in oscillation mode In Methods in Enzymology; Carter, C. W., Jr.,
Sweet, R. M., Eds.; Macromolecular Crystallography, Part A; Academic Press:
London, 1997; Vol. 276, p 307.
10. Zhu, Z.; Drach, J. C.; Townsend, L. B. J. Org. Chem. 1998, 63, 977.
11. Duffy, K. J.; Price, A. T.; Delorme, E.; Dillon, S. B.; Duquenne, C.; Miller, C. M.;
Giampa, L.; Huang, Y.; Keenan, R. M.; Lamb, P.; Liu, N.; Miller, S. G.; Rosen, J.;
Shaw, A. N.; Smith, H.; Wiggall, K. J.; Zhang, L.; Luengo, J. I. J. Med. Chem. 2002,
54, 3576.
30. SIR97- Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.; Giacovazzo, C.;
Guagliardi, V.; Moliterni, A. G. G.; Polidori, G.; Spagna, R. J. Appl. Crystallogr.
1999, 32, 115.
12. Tseng, C. H.; Lin, C. S.; Shih, P. K.; Tsao, L. T.; Wangd, J. P.; Cheng, C. M.; Tzeng, C.
C.; Chen, Y. L. Bioorg. Med. Chem. 2009, 17, 6773.
31. Sheldrick, G. M. Acta Cryst. A 2008, A64, 112.