A [5 + 1] annulation strategy for the synthesis of multifunctional biaryls and: P -teraryls from 1,6-Michael acceptor ketene dithioacetals

Article abstract of DOI:10.1039/d0ob00998a

A new type of ketene dithioacetal, 2-(3,3-bis-methylsulfanyl-1-arylallylidene)malononitriles containing 1,4 and 1,6-Michael acceptors, were synthesized to study their reactivity for the synthesis of a new molecular entity. We report a [5 + 1] annulation s

Full text of DOI:10.1039/d0ob00998a

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ARTICLE
[5+1] Annulation strategy for the synthesis of
multifunctional biaryls and p-teraryls from 1,6-Michael
acceptor ketene dithioacetals
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Shally,a Ismail Althagafi,b Ranjay Shaw,a Amr Elagamy,a Abhinav Kumarc and Ramendra Pratapa,*
A new type of ketene dithioacetal, 2-(3,3-bis-methylsulfanyl-1-arylallylidene)malononitriles containing 1,4 and 1,6-
Michael acceptor was synthesized to study their reactivity for the synthesis of new molecular entity. We are reporting
[5+1] annulation strategy for the construction of multifunctional biaryls and p-teraryls by selection of suitable nucleophile
source. The reaction of p-nitrotoluene with 2-(3,3-bis-methylsulfanyl-1-aryl-allylidene)-malononitriles under basic
conditions provides p-teraryls in good yields, while use of nitroethane as nucleophile source provides functionalized biaryls
through cyclization followed by denitration. The reaction requires mild condition and exhibit good functional group
tolerance.
Introduction
Naturally occurring biaryls
Ketene dithioacetals are important precursor in organic
synthesis and broadly used as multifaceted synthone1 for
assembly of large class of carbocyclic and heterocyclic
compound due to the presence of conjugated double bond,
which can react with both nucleophiles and electrophiles.2 Due
to great synthetic potential of ketene dithioacetal, various
researchers are involved in the exploration of their chemistry.3
They can undergo addition, substitution and elimination
reactions simultaneously and therefore used as promising
precursor for the synthesis of different class of molecules.4 Our
research group had recently reported the assembly of
imidazo[1,2-a]pyridines and aroylnaphthalenes moiety from
ketene dithioacetals using the 4+2 and 5+1 annulation
strategy.5,6 There are a variety reactions reported from ketene
dithioacetal, where reaction starts with 1,4-addition followed
by cyclization and aromatization. Earlier our research group
explored the synthesis of naphthalenes by [5+1] annulations
using ketene dithioacetal of 2–cyanometylbenzonitrile (1,6-
Michael acceptor). Therefore, we became interested to
synthesized another ketene dithioacetal,6 which can undergo
1,6-Michael addition and cyclization reaction and 2-(1-aryl-3,3-
bis(methylthio)allylidene)malononitriles was design and
synthesized.
OMe
OH
MeO
OMe
HO
O
O
H2N
H2N
OH
OH
O
HN
OMe
NH
HO
OH
Aurasperone A
O(Antifungal activity)
O
O
O
Biphenomycin
(Antibiotic)
OH
OH
OH
HO
HO
OH
Magnolol
Clusiparalicolines A
(Cytotoxiccity activity)
(Neurotrophic activity)
Naturally occurring p-teraryls
OH
HO
OH
MeO
HO
HO
HO
OAc
OAc
AcO
AcO
HO
HO
OAc
OAc
OMe
OMe
O
OH
Sarcodon
(Immunological activity)
OH
Terferol
(Parasite inhibitor)
Prenylterphenyllin D
(Antimicrobial activity)
Sarcoviolin
(Antioxidant activity)
a. Department of Chemistry, University of Delhi, North Campus, Delhi-110007
India.E-mail: rpratap@chemistry.du.ac.in; ramendrapratap@gmail.com; Tel: +91
1127666646
Figure 1. Structure of representative biaryl and p-teraryl
b. Department of Chemistry, Umm Al-Qura University, Makkah, Saudi Arabia
c. Department of Chemistry, University of Lucknow, Lucknow, Uttar Pradesh-226009
India
derived natural compounds
Biaryls and teraryls are valuable structural moieties and
various synthetic approaches have been established for their
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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Journal Name
View Article tOhnelinier
7
assembly. They are elite entities and present as substructure of malononitrile but it was difficult to afford and
in various molecules of medicinal and material importance.8 synthetic protocol are under investigatioDnO. I: 10.1039/D0OB00998A
Biaryls and p-teraryls scaffolds are also present as substructure
in various natural products, such as biphenomycin,
Table
1.
Synthesis
of
various
2-(3,3-bis(methylthio)-1-
aurasperone A, clusiparalicolines A, magnolol, terferol,
sarcodan, sarcoviolin, prenylterphenyllin D and concrescens A
(Figure 1).9-10 Biaryls are also present as basic skeleton in
pharmaceutically active compounds, light-emitting diodes,
herbicides; liquid crystal and metal ligand.11 Besides p-teraryl
based compounds are reported for the industrial application as
conducting polymers, liquid crystals, cation sensors, and
dyes.12
arylallylidene)malononitriles (2)
CN
NC
Ar
CN
NC
CN
CS2/CH3I
O
CN
NH4OAc/CH3COOH
NaH/THF
0-5 oC
Ar
Ar
MeS
SMe
1
2
Suitably aminated teraryls are also useful for the synthesis of
biologically and pharmaceutically important compound like
carbazoles, estrogen receptors, anti-HIV agent siamenol and
antihyperglycemic agents.13
Entry
R
Yield of 2 (%)
2a
2b
2c
2d
2e
2f
2g
2h
2i
C6H5
96
98
96
98
94
83
92
91
78
85
92
90
70
74
90
94
92
60
p-CH3.C6H4
p-NH2.C6H4
p-OMe.C6H4
In general, synthesis of biaryls and teraryls are carried out by
various transition metal catalyzed aryl-aryl bond formation
reactions.14 Another approach is assembly of benzene ring by
cycloaddition reactions using aryl containing open chain
precursors.15 Various benzannulation strategies was
developed for the construction of polyfunctionalized
benzenes such as [3+2+1] Dӧtz reaction of Fisher carbene
complexes, Danheiser alkyne-cyclobutenone [4+2] cyclization,
[4+2] cycloaddition of metal cyclopentadiene and alkynes,
transition-metal catalyzed [2+2+2] and [4+2] cycloadditions,
[4+2] Yamamoto benzannulation of o-alkynyl benzaldehyde
and alkyne, [3+3] cyclocondensation between biselectrophiles
and bisnucleophiles, and 1,6-electrocyclization reaction.16
However, these approaches suffer with some drawback with
respect to environmental concern or atom economy, multi-
3,4-(OCH3)2.C6H3
o-OCH3.C6H4
p-F.C6H4
p-Cl.C6H4
2,4-Cl2.C6H3
o-Cl.C6H4
p-Br.C6H4
m-Br.C6H4
2-Furyl
2j
2k
2l
2m
2n
2o
2p
2q
2r
2-Thienyl
1-Naphthyl
2-Naphthyl
p- C6H5.C6H4
Cyclopropyl
For the synthesis of 2; All reactions were performed by stirring 1 (10 mmol), CS2 (11
mmol), CH3I (22 mmol) and NaH (20 mmol) in THF (50.0 mL) at 0-5oC for 5 hours and
steps and low yields of products. On the other hand metal- yields are reported only for the second step of the reaction.
assisted cross-coupling reactions also suffer from the
requirements for expensive organometallic reagents/catalysts,
harsh reaction conditions and undesired side-products.
Herein, we used new ketene dithioacetal for generation of
multifunctional biaryls and p-teraryls under mild condition.
Synthesis of various multifunctional biaryls and p-teraryls
Once, we had precursors in our hand, reaction condition was
optimized for the synthesis of p-teraryls. To optimize the
reaction
condition,
2-(3,3-bismethylsulfanyl-1-p-tolyl-
allylidene)-malononitrile (2b) and 4-nitrotoluene were chosen as
model substrates. We started the study using Et3N, NaOH and KOH
as a base in DMF at room temperature and both the starting
materials were left unreacted (Table 2, entries 1-3). The use of KOH
in DMF at 60 oC provides the desired p-teraryl in 65% yield (Table 2,
entry 4), while increasing the temperature to 90 oC drop the yield to
50% (Table 2, entry 5). We further screened KOH in DMSO at room
temperature and no product was obtained (Table 2, entry 6), while
at 60 oC, the desired product was isolated in 45% yield (Table 2,
Results and discussion
Preparation of precursor 2-(3,3-bis(methylthio)-1-aryl-
allylidene)malononitriles
To start our study, we synthesized the required precursors 2-
(3,3-bis(methylthio)-1-aryl-allylidene)malononitriles. The first
step was the synthesis of (1-arylethylidene)malononitriles by
condensation reaction of aryl methyl ketone and malononitrile
in presence of glacial acetic acid and ammonium acetate in
toluene under reflux condition.17 In the second step, 2-(1-
arylethylidene)malononitriles was treated with carbon
disulphide and methyl iodide under basic conditions to afford
the desired precursor (2) in 60-98% yield (Table 1). Trial of
many solvent and base combinations demonstrated that
sodium hydride (NaH) in THF at 0-5 oC act as best combination
(See ESI, Table 1).
o
entry 7). Then, we used NaH in DMSO and DMF at 60 C and the
product was obtained in 29 and 33% yield respectively (Table 3.1,
entries 8 and 9). The use of Cs2CO3 and NaNH2 in DMF at 60 oC
provides no product and the starting materials were left unreacted
(Table 2, entries 10 and 11). Furthermore, conducting the reaction
using KOH in non-polar solvent such as dioxane, toluene and THF
under reflux condition provided no product and the starting
material (2) underwent hydrolysis (Table 2, entries 12-14). The
o
optimization shows that, KOH in DMF at 60 C is the best reaction
In addition, we also tried to synthesize 1,6 Michael acceptor
using dialkyl malonate and methyl/ethyl cyanoacetate instead
conditions for the synthesis of multi-functionalized p-teraryls. With
2 | J. Name., 2012, 00, 1-3
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optimal conditions in hand, the generality of the protocol was In addition, we tried the reaction of 2-(1-([1,1'-biphenyl]-4-yl)-3,3-
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DOI: 10.1039/D0OB00998A
tested by using various functionalized ketene dithioacetals and bis(methylthio)allylidene)malononitrile (2q) with 1-methyl-4-
commercially available 1-methyl-4-nitrobenzene, 2-bromo-1- nitrobenzene under optimized reaction condition and afforded
methyl-4-nitrobenzene and 2-chloro-1-methyl-4-nitrobenzene linear quateraryl (4k) in 47% yield. The structure of 3'-amino-4-
(Table 3). It was found that, the reaction provides multi- bromo-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
functionalized p-teraryls in moderate yields in all cases, however a carbonittrile (4h) was confirmed by single-crystal X-ray analysis.
relatively lower yield was observed when 2-substituted-1-methyl-4-
nitrobenzene (4k, 4l and 4m) and functionalized ketene
dithioacetals bearing 2-substituted phenyl group (4e) was used
probably due to steric hindrance effect. On the other hand, the
Table 3. Synthesis of various multifunctional p-teraryls (4)a
CH3
NO2
X
reaction
of
2-(1-furan/thiophen-2-yl)-3,3-
with 1-methyl-4-
X = H, Cl, Br
bis(methylthio)allylidene)malononitriles
X
NC
CN
nitrobenzene under same reaction conditions provides no product.
NO2
3
H2N
SMe
SMe
SMe
R2
R1
Table 2. Optimization of the reaction conditions 4a
KOH/DMF
60 oC/5 h
NC
R2
2
NO2
R1
4
CH3
NC
CN
NO2
SMe
H2N
NC
NO2
SMe
SMe
Base/solvent
temp.
NO2
Br
H3C
2
H2N
SMe
H2N
NC
SMe
3
4
CH3
NC
Ar
Entry
Base
Solvent
Temp.(oC)
Time (h)
Yield
(%)b
4a. Ar = C H ; 60%
6
5
4b. Ar = 4-CH C H ; 65%
3
6 4
Ph
4c. Ar = 4-OCH C H ; 55%
c
3
6 4
1
2
Et3N
NaOH
KOH
DMF
DMF
r.t
r.t
24
24
24
5
-
4d. Ar = 3,4-(OCH ) C H ; 53%
3 2
6 3
4k, 47%
4e. Ar = 2-OCH C H ; 42%
c
3 6 4
-
4f. Ar = 4-FC H ; 50%
6
4
4g. Ar = 4-ClC H ; 50%
6
4
c
3
DMF
r.t
-
4h. Ar = 4-BrC H ; 52%
6
4
4i. Ar = 3-BrC H ; 48%
6
4
4
KOH
DMF
60
65
50
4j. Ar = 2-Naphthyl; 45%
5
KOH
DMF
90
7
NO2
NO2
NO2
c
6
KOH
DMSO
DMSO
DMSO
DMF
r.t
24
9
-
Br
7
KOH
60
45
29
33
Cl
Br
H2N
SMe
H2N
SMe
SMe
H2N
8
NaH
60
18
18
24
24
12
12
NC
NC
9
NaH
60
NC
c
10
11
12
13
Cs2CO3
NaNH2
KOH
DMF
60
-
c
DMF
60
-
CH3
4n, 42%
4l, 41%
4m 40%
d
Dioxane
Toluene
Reflux
Reflux
-
d
Reaction conditions:All reaction were carried out by stirring 2 (0.5 mmol),
KOH
-
(0.5 mmol), KOH (1 mmol) in DMF (4.0 mL) at 60 oC
d
14
KOH
THF
Reflux
12
-
To further expand the scope of this methodology, we have
2-(3,3-bis(methylthio)-1- employed nitroethane as nucleophile source. He reaction condition
aAll
reaction
were
performed
by
stirring
arylallylidene)malononitrile (2) (0.5 mmol), 1-methyl-4-nitrobenzene (3) (0.5 mmol)
and base (1 mmol) in solvent (4 mL) at room temperature and high temperature. (b)
Room temperature was ranging between 40-45 oC and high temperature 60-90 oC; (c)
Both the starting materials were left in the reaction mixture; (d) Compound (2)
underwent hydrolysis.
was optimized by using different base and solvent combinations
(see ESI, Table 2). It was observed that use of potassium hydroxide
in DMF at 45 oC act as best reaction condition. The generality of
protocol was tested by using diferent 2-(3,3-bis(methylthio)-1-
arylallylidene)malononitriles (2) to afford 3-amino-4-methyl-5-
(
methylthio)-[1,1'-biphenyl]-2-carbonitriles (6) in moderate to
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good yields (Table 4). It was observed that, substituents such as Me, of excess of base, intermediate B generates the carbanion which
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DOI: 10.1039/D0OB00998A
OMe, F, Cl and Br on the phenyl ring of the ketene dithioacetals are intramolecularly attacks at one of the nitrile group with the
well tolerated during the reaction.
formation of imine C. Intermediate C undergoes tautomerization to
2-Naphthyl and biphenyl containing ketene dithioacetals were also afford the desired teraryl 4.
examined and the desired products obtained in 61% and 62% yields
Scheme 1. Plausible mechanism for the synthesis of multifunctional p-teraryls and
biaryls
respectively. Interestingly, when nitromethane was used as a
nucleophile source in lieu of nitroethane, a complex mixture was
obtained. Nitromethane might be involved in other side reactions
(interact at other double bond) probably due to its small size and
higher reactively as compared to nitroethane.
CH3
NC
Ar
CN
SMe
SMe
2
C2H5NO2
Path B
NO2
KOH
KOH
Path A
NO2
CH2
Table 4. Synthesis of multifunctional biarylsa
NH2
N
CH3
HC
NC
CN
NC
Ar
C
NC
CH3
SMe
N
DMF/KOH
45 oC/1 h
SMe
SMe
SMe
NC
C
C2H5NO2
NO2
R2
R1
R2
SMe
SMe
+
SMe
5
2
Ar
6
R1
CH3
CH3
CH3
CH3
N
N
NC
Ar
C
H2N
SMe
H2N
SMe H2N
NC
SMe H2N
SMe
NC
Ar
C
SMe
SMe
SMe
NC
NC
NC
SMe
A
NO2
D
H3C
R
OMe
-SMe
-SMe
OMe
CH3
OMe
6c, 65%
6a, 70%
6b, 72%
6d, 48%
NC
CN
R
NC
CN NO2
CH3
CH3
CH3
CH3
CH3
H2N
NC
SMe
H2N
NC
SMe
H2N
SMe
H2N
NC
SMe
Ar
SMe
Ar
SMe
B
E
NC
Cl
OMe
-H+ KOH
-H+ KOH
6e, 49%
Cl
F
Br
6h, 55%
N
N
6g, 50%
6f, 52%
CH3
NC
Ar
C
R
CH3
NC
Ar
C
NO2
CH3
SMe
CH3
SMe H2N
SMe
H2N
SMe
H2N
NC
SMe
NC
NC
+H+
+H+
NH
NH
NC
Ar
R
Br
NC
Ar
CH3
NO2
SMe
Ph
6k, 62%
OH
H
6i, 49%
6j, 61%
SMe
C
F
[Reaction conditions: All reaction was carried out by stirring 2 (0.5 mmol), 5
(0.5 mmol) and KOH (1 mmol) in DMF (4.0 mL) at 45oC].
+H+
-HNO3
Tautomerization
Tautomerization
NH2
NH2
Mechanistic Investigation
NC
Ar
CH3
SMe
NC
Ar
R
R=
On the basis of the product formed, we proposed that the
formation of both biaryl and teraryl by the reaction of nitroethane
and p-nitrotoluene follows two different pathways (Scheme 1). The
precursor 2-(3,3-bis(methylthio)-1-arylallylidene)malononitriles has
two electrophilic centers at the C-1 and C-3 position. Among them
C-3 is highly vulnerable in case of using large nucleophiles. For the
synthesis of teraryls, reaction starts with generation of carbanion
from p-nitrotoluene under basic conditions. Mechanistically,
reaction is possibly initiated through attack of nucleophile at the C-
3 position of 2-(3,3-bis(methylthio)-1-arylallylidene)malononitriles
(2) to form intermediate A, which was converted to intermediate B
by reversal of the charge and elimination of SMe group. In presence
SMe
NO2
6
4
If nitroethane is used as nucleophile source, reaction follows path
B. Under basic condition carbanion generated from nitroethane
undergoes 1,6-addition reaction to form intermediate D, which was
converted to intermediate E by loss of methanthiol group. In
presence of excess of base carbanion generated at carbon adjacent
to nitro group, which cyclize intramolecularly using nitrile group to
afford imine F. At last, excess of hydroxide ion attacks at nitrogen of
4 | J. Name., 2012, 00, 1-3
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nitro group of intermediate F to afford aromatization by loss of
nitric acid.
To understand the role of base, we perform the control
Experimental
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General: Commercially available reagenDtsOIf:r1o0m.10S39ig/Dm0aOBA0ld09ri9c8hA,
Alfa Aesar and Spectrochem were used directly. 1H and 13C
NMR spectra were recorded using 400 MHz NMR and 100 MHz
NMR spectrometer and CDCl3 was used as solvent. Chemical
shifts for all the compounds are reported in parts per million
reaction
between
2-(3,3-bis(methylthio)-1-phenyl-
allylidene)malononitrile and p-nitrotoluene without base and no
product was observed and starting material was left
unconsumed (Scheme 5). This suggests that base is required
for the reaction. In another reaction, 2-(3,3-bis(methylthio)-1-
phenyl-allylidene)malononitrile was treated with KOH in DMF and
afforded 3,3-bis-methylsulfanyl-1-phenyl-propenone in good yield.
This suggests that C-1 position is also reactive and interact with
nucleophile depending on their nature. In another trial 3,3-bis-
methylsulfanyl-1-phenyl-propenone was treated with malononitrile
under basic condition provides 1,6-Michael acceptor 2H-pyran-2-
ones instead of compound 2. This reaction suggests that compound
2 can be exclusively synthesized from 2-(1-phenyl-ethylidene)-
malononitrile obtained by reaction of acetophenone with
malononitrile, which on treatment with carbon disulfide and methyl
iodide provides compound 2.
1
shifts (δ-value) from CDCl3 (δ 7.26 ppm for H and 77.00 ppm
for 13C NMR) as an internal standard. In 1H NMR signal
patterns are reported as s, singlet; d, doublet; dd, double
doublet; t, triplet and m, multiplet. Coupling constant (J) for
protons are reported in hertz (Hz). Infrared (IR) spectra of all
the compounds was recorded on a Perkine Elmer AX-1
spectrophotometer and reported in wave number (cm-1).
HRMS reported are showing the peak for MH+.
General procedure for the synthesis of 2-(3,3-bis(methylthio)-1-
arylallylidene)malononitriles 2a-r: To a vacuum dried RB flask
sodium hydride (20.0 mmol) was taken in dry THF (50.0 mL) and
cooled to 0-5 oC over an ice bath. Then 2-(1-
arylethylidene)malononitriles (10.0 mmol) was added slowly within
45 minutes with constant stirring at 0-5 oC and the reaction mixture
was further stirred for 25-30 minutes. To this solution carbon
disulfide (11 mmol) was added drop-wise within 25-30 minutes and
the mixture was again stirred for 25-30 minutes. Further, methyl
Further reaction of this compound is under investigation with
various other nucleophiles.
Scheme 5. Control reaction for the reactivity of compound 2
CH3
o
iodide (22 mmol) was added drop-wise at 0-5 C and continued the
NC
Ar
CN
stirring for another 30 minutes. Then, the reaction mixture was
warmed slowly to room temperature and stirred for 3 hours. After
completion of the reaction (determined by TLC), excess of THF was
removed under reduced pressure and crushed ice was added to the
reaction mixture. The obtained precipitate was filtered, dried and
recrystallized with cold ethanol.
2-(3,3-Bis(methylthio)-1-phenylallylidene)malononitrile (2a)
Brown solid; yield: 2.62 g, (96%); mp = 180–182 °C; IR (KBr):
2921, 2215, 1429-1607 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.32
(s,3H, -SMe), 2.60 (s, 3H, -SMe), 6.48 (s, 1H, ArH), 7.27-7.30 (m,
2H, ArH), 7.43-7.46 (m, 3H, ArH); 13C NMR (100 MHz, CDCl3): δ
16.4, 17.7, 77.7, 113.1, 113.8, 114.2, 129.5, 130.0, 132.7,
137.5, 165.8, 166.4; HRMS (ESI): m/z [M + H]+ calcd for
C14H13N2S2: 273.0515; found: 273.0519.
No base
+
No reaction
MeS
SMe
CN
NO2
2
NC
Ar
KOH
DMF
SMe
SMe
O
SMe
SMe
Ar
7
2
SMe
NC
Ar
CN
NC
O
O
SMe
CH2(CN)2
CH2(CN)2
SMe
X
Ar
O
8
Ar
7
MeS
SMe
2
2-(3,3-Bis(methylthio)-1-(p-tolyl)allylidene)malononitrile (2b)
Yellow solid; yield: 2.80 g (98%); mp = 92–95 °C; IR (KBr): 2921,
2215, 1429-1607 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.30 (s,3H, -
CH3), 2.41 (s, 3H, -SMe), 2.59 (s, 3H, -SMe), 6.49 (s, 1H, ArH), 7.22-
7.30 (m, 4H, ArH); 13C NMR (100 MHz, CDCl3): δ 16.5, 17.6, 21.6,
77.4, 114.0, 114.2, 114.5, 128.6, 129.8, 131.5, 142.0, 164.4, 168.1;
HRMS (ESI): m/z [M + H]+ calcd for C15H15N2S2: 287.0671; found:
287.0666.
Conclusions
In summary, we used 1,6-Michael acceptor ketene
dithioacetals for developing a new methodology to synthesize
highly substituted biaryls and p-teraryls. The reaction of p-
nitrotoluene and nitroethane with 2-(3,3-bis-methylsulfanyl-1-
aryl-allylidene)-malononitriles under basic conditions provides
p-teraryls and biaryls respectively in good yields. This reaction
requires mild condition and shows good functional group
tolerance. We also tried to explained the mechanism. We have
exclusively perform 1,6-addition over 1,4-Michael addition. In
addition we also demonstrated that hydroxide ion act as
nucleophile in absence of proton source ad provides 1,4-
Michael addition to afford loss of malononitrile. Further
chemistry of the ketene dithioacetals are under investigation.
2-(1-(4-Aminophenyl)-3,3-bis(methylthio)allylidene)-
malononitrile (2c)
Yellow solid; yield: 2.77 g (96%); mp = 100–105 °C; IR (KBr):
2925, 2215, 1435-1568 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.28
(s, 3H, -SMe), 2.54 (s, 3H, -SMe), 4.13 (s, 2H, -NH2), 6.39 (s, 1H,
ArH), 6.66 (d, J = 8 Hz, 2H, ArH), 7.24 (s, 2H, ArH); 13C NMR
(100 MHz, CDCl3): δ 16.8, 17.7, 75.1, 114.7, 115.0, 115.5,
123.7, 130.5, 131.4, 150.6, 161.8, 168.3; HRMS (ESI): m/z [M +
H]+ calcd for C14H14N3S2: 288.0624; found: 288.0629.
This journal is © The Royal Society of Chemistry 20xx
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113.7, 128.3, 130.5, 130.5, 132.4, 133.6, 137.5, 162.7, 166.6;
2-(1-(4-Methoxyphenyl)-3,3-bis(methylthio)allylidene)-
malononitrile (2d)
View Article Online
DOI: 10.1039/D0OB00998A
+
HRMS (ESI): m/z [M + H] calcd for C14H11Cl2N2S2: 340.9735;
Brown solid; yield: 2.98 g (98%); mp = 105–107 °C; IR (KBr): found: 340.9733.
2925, 2215, 1435-1568 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.31 2-(1-(2-Chlorophenyl)-3,3-bis(methylthio)allylidene)-
(s,3H, -SMe), 2.59 (s, 3H, -SMe), 3.87 (s, 3H, -OMe), 6.46 (s, 1H, malononitrile (2j)
ArH), 6.97 (d, J = 8 Hz, 2H ArH), 7.34 (d, J = 8 Hz, 2H ArH); 13C Brown solid; yield: 2.62 g (85%); mp = 93–95 °C; IR (KBr): 3088,
NMR (100 MHz, CDCl3): δ 16.6, 17.6, 55.3, 72.7, 114.3, 114.4, 2925, 2207, 1427-1585 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.33
114.5, 114.8, 126.4, 130.7, 162.4, 163.8, 167.8; HRMS (ESI): (s,3H, -SMe), 2.60 (s, 3H, -SMe), 6.55 (s, 1H, ArH), 7.19 (dd, J =
m/z [M + H]+ calcd for C15H15N2OS2: 303.0620; found: 1.2 Hz, J = 7.2 Hz, 1H, ArH), 7.36 (td,J = 2.0 Hz, J = 7.6 Hz,
303.0626.
1H,ArH), 7.41 (dd, J = 1.6 Hz, J = 8.0 Hz, 1H,ArH), 7.43-7.47 (m,
1H,ArH); 13C NMR (100 MHz, CDCl3): δ 16.5, 17.8, 78.1, 112.5,
113.7, 114.0, 127.8, 129.7, 130.4, 132.0, 132.6, 134.0, 164.0,
2-(1-(3,4-Dimethoxyphenyl)-3,3-bis(methylthio)allylidene)-
malononitrile (2e)
Brown solid; yield: 3.14 g (94%); mp = 120–122 °C; IR (KBr): 166.0; HRMS (ESI): m/z [M + H]+ calcd for C14H12ClN2S2:
3002, 2959, 2213, 1423-1596 cm–1; H NMR (400 MHz, CDCl3): 307.0125; found: 307.0129.
1
δ 2.32 (s,3H, -SMe), 2.60 (s, 3H,- SMe), 391 (s, 3H, -OMe), 3.95 2-(1-(4-Bromophenyl)-3,3-bis(methylthio)allylidene)-
(s, 3H, -OMe), 6.47 (s, 1H, ArH), 6.88-7.01 (m, 3H, ArH); 13C malononitrile (2k)
NMR (100 MHz, CDCl3): δ 16.6, 17.6, 55.9, 56.1, 79.4, 111.2, Brown solid; yield: 3.22 g (92%); mp = 98–100 °C; IR (KBr):
1
111.7, 114.0, 114.4, 115.0, 122.5, 126.5, 149.3, 152.0, 164.0, 3054, 2923, 2215, 1427-1587 cm–1; H NMR (400 MHz, CDCl3):
167.6; HRMS (ESI): m/z [M + H]+ calcd for C16H17N2O2S2: δ 2.33 (s,3H, -SMe), 2.61 (s, 3H, -SMe), 6.48 (s, 1H, ArH), 7.22
333.0726; found: 333.0726.
(d, J = 8.4 Hz, 2H, ArH), 7.61 (d, J = 8.4 Hz, 2H, ArH); 13C NMR
(100 MHz, CDCl3): δ 16.0, 16.5, 77.7, 113.1, 113.8, 114.1,
126.0, 130.1, 132.5, 133.3, 165.8, 166.4; HRMS (ESI): m/z [M +
2-(1-(2-Methoxyphenyl)-3,3-bis(methylthio)allylidene)-
malononitrile (2f)
Brown solid; yield: 2.51 g (83%); mp = 115–117 °C; IR (KBr): H]+ calcd for C14H12BrN2S2: 350.9620; found: 350.09607.
3002, 2925, 2214, 1429-1599 cm–1; H NMR (400 MHz, CDCl3): 2-(1-(3-Bromophenyl)-3,3-bis(methylthio)allylidene)-
1
δ 2.31 (s,3H, -SMe), 2.60 (s, 3H, -SMe), 3.86 (s, 3H, -OMe), 6.55 malononitrile (2l)
(s, 1H, ArH), 6.97 (d, J = 8 Hz, 1H, ArH), 7.01-7.08 (m, 2H, ArH), Brown solid; yield: 3.15 g (90%); mp = 120–122 °C; IR (KBr): 2958,
1
7.45 (t, J = 8 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ 16.3, 2854, 2214, 1425-1557 cm–1; H NMR (400 MHz, CDCl3): δ 2.34
17.6, 55.8, 78.1, 111.7, 113.5, 114.1, 114.4, 121.2, 123.6, (s,3H, -SMe), 2.61 (s, 3H, -SMe), 6.48 (s, 1H, ArH), 7.29 (d, J = 8.4
129.3, 132.3, 156.4, 164.1, 164.6; HRMS (ESI): m/z [M + H]+ Hz, 1H, ArH), 7.36 (t, J = 7.6 Hz, 1H,ArH), 7.46 (s, 1H, ArH), 7.64 (d, J
calcd for C15H15N2OS2: 303.0620; found: 303.0624.
2-(1-(4-Fluorophenyl)-3,3-bis(methylthio)allylidene)-
malononitrile (2g)
= 7.6 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ 16.6, 17.7, 78.0,
113.0, 113.7, 114.0, 123.0, 127.1, 130.7, 131.2, 134.0, 136.3, 165.6,
166.3; HRMS (ESI): m/z [M + H]+ calcd for C14H12BrN2S2: 350.9620;
Brown solid; yield: 2.67 g (92%); mp = 95–97 °C; IR (KBr): 2923, found: 350.9628.
2216, 1435-1568 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.42 (s,3H, 2-(1-(Furan-2-yl)-3,3-bis(methylthio)allylidene)malononitrile
-SMe), 2.54 (s, 3H, -SMe), 6.27 (s, 1H, ArH), 6.64 (dd, J = 1.2 Hz, (2m)
J = 3.6 Hz, 2H,ArH), 7.21 (d, J = 4 Hz, 1H,ArH), 7.71 (d, J = 1.6 Brown solid; yield: 1.52 g (70%); mp = 45–47 °C; IR (KBr): 3054,
Hz, 1H,ArH); 13C NMR (100 MHz, CDCl3): δ 16.4, 17.7, 77.7, 2213, 1427-1650 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.42 (s,3H,
113.4, 114.0, 114.2, 116.5 (d, JC-F = 20 Hz), 130.3, 130.8 (d, JC-F -SMe), 2.54 (s, 3H, -SMe), 6.27 (s, 1H, ArH), 6.57 (dd, J = 2 Hz, J
= 20 Hz), 163.2, 165.6 (d, JC-F = 20 Hz), 166.6; HRMS (ESI): m/z = 3.6 Hz, 1H, ArH), 7.22 (d, J = 3.6 Hz, 1H,ArH), 7.71-7.71 (m,
[M + H]+ calcd for C14H12FN2S2: 291.0420; found: 291.0422.
2-(1-(4-Chlorophenyl)-3,3-bis(methylthio)allylidene)-
malononitrile (2h)
1H, ArH); 13C NMR (100 MHz, CDCl3): δ 17.1, 17.6, 75.2, 113.6,
114.1, 114.3, 114.7, 120.3, 147.5, 148.0, 153.3, 158.5; HRMS
(ESI): m/z [M + H]+ calcd for C12H11N2OS2: 263.0307; found:
Brown solid; yield: 2.80 g (91%); mp = 100–102 °C; IR (KBr): 2922, 263.0314.
1
2215, 1428-1588 cm–1; H NMR (400 MHz, CDCl3): δ 2.33 (s,3H, - 2-(3,3-Bis(methylthio)-1-(thiophen-2-yl)allylidene)malono-
SMe), 2.60 (s, 3H, -SMe), 6.48 (s, 1H, ArH), 7.22 (d, J = 8.8 Hz, nitrile (2n)
1H,ArH), 7.29 (d, J = 8.8 Hz, 1H,ArH), 7.45 (d, J = 8.8 Hz, 1H, ArH), Brown viscous; yield: 1.72 g (74%); mp = 53–55 °C; IR (KBr):
7.61 (d, J = 8.8 Hz, 1H,ArH); 13C NMR (100 MHz, CDCl3): δ 16.5, 2923, 2213, 1410-1596 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.39
17.7, 77.7, 113.1, 113.8, 114.1, 129.5, 130.0, 130.1, 132.5, 165.8, (s,3H, -SMe), 2.55 (s, 3H, -SMe), 6.39 (s, 1H, ArH), 7.18-7.20 (m,
166.4; HRMS (ESI): m/z [M + H]+ calcd for C14H12ClN2S2: 307.0125; 1H, ArH), 7.69 (dd, J = 5.6 Hz, J = 13.2 Hz, 2H ArH); 13C NMR
found: 307.0135.
2-(1-(2,4-Dichlorophenyl)-3,3-bis(methylthio)allylidene)-
malononitrile (2i)
(100 MHz, CDCl3): δ 17.0, 17.5, 76.2, 114.0, 114.4, 116.5,
128.7, 133.0, 133.4, 136.6, 159.8, 160.3; HRMS (ESI): m/z [M +
H]+ calcd for C12H11N2S3: 279.0079; found: 279.0083.
Brown solid; yield: 2.65 g (78%); mp = 93–95 °C; IR (KBr): 3083, 2-(3,3-Bis(methylthio)-1-(naphthalen-1-yl)allylidene)malono-
2922, 2215, 1427-1586 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.39 nitrile (2o)
(s,3H, -SMe), 2.62 (s, 3H, -SMe), 6.54 (s, 1H, ArH), 7.15 (d, J = Brown solid; yield: 2.90 g (90%); mp = 103–105 °C; IR (KBr):
1
8.4 Hz, 1H,ArH), 7.37 (d, J = 8.0 Hz, 1H,ArH), 7.50 (s, 1H,ArH); 3054, 2924, 2213, 1427-1650 cm–1; H NMR (400 MHz, CDCl3):
13C NMR (100 MHz, CDCl3): δ 16.5, 17.8, 78.3, 112.3, 113.5, δ 2.22 (s,3H, -SMe), 2.63 (s, 3H, -SMe), 6.59 (s, 1H, ArH), 7.40
6 | J. Name., 2012, 00, 1-3
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HRMS (ESI): m/z [M + H]+ calcd for C20H16N3O2S: 362.0958; found:
(d, J = 8 Hz, 1H, ArH), 7.55-7.61 (m, 2H, ArH), 7.88-7.94 (m, 4H,
ArH); 13C NMR (100 MHz, CDCl3): δ 17.0, 17.8, 78.1, 113.3,
114.2, 114.3, 123.8, 125.7, 126.6, 126.8, 127.5, 128.7, 130.6,
131.1, 132.4, 133.7, 166.2, 166.4; HRMS (ESI): m/z [M + H]+
calcd for C18H15N2S2: 323.0671; found: 323.0677.
View Article Online
DOI: 10.1039/D0OB00998A
362.0958.
3'-Amino-4-methyl-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
carbonitrile (4b)
Brown solid; yield: 123 mg (65%); mp = 110–112 °C; IR (KBr): 3480,
2925, 2215, 1425-1560 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.39
(s,3H, -CH3), 2.43 (s, 3H, -SMe), 4.26 (s, 2H, -NH2), 6.65 (s, 1H, ArH),
7.31 (d, J = 12 Hz, 2H, ArH), 7.49 (d, J = 8 Hz, 2H, ArH), 7.53 (d, J = 12
Hz, 2H, ArH), 8.40 (d, J = 8 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3):
δ 15.2, 21.2, 114.1, 117.5, 120.2, 124.8, 128.3, 129.4, 131.7, 135.6,
139.0, 141.7, 145.1, 145.2, 146.0, 147.0, 148.0; HRMS (ESI): m/z [M
+ H]+ calcd for C21H18N3O2S: 376.1114; found: 376.1118.
2-(3,3-Bis(methylthio)-1-(naphthalen-2-yl)allylidene)malono-
nitrile (2p)
Brown solid; yield: 3.05 g (94%); mp = 110–112 °C; IR (KBr):
1
3054, 2924, 2213, 1427-1650 cm–1; H NMR (400 MHz, CDCl3):
δ 2.21 (s,3H, -SMe), 2.63 (s, 3H, -SMe), 6.59 (s, 1H, ArH), 7.40
(d, J = 12 Hz, 1H,ArH), 7.35-7.60 (m, 2H, ArH), 7.88-7.94 (m, 4H,
ArH); 13C NMR (100 MHz, CDCl3): δ 16.5, 17.7, 77.8, 113.8,
114.2, 114.5, 124.1, 125.1, 126.8, 127.8, 128.8, 129.0, 129.1,
131.8, 133.0, 134.3, 165.2, 166.7; HRMS (ESI): m/z [M + H]+
calcd for C18H15N2S2: 323.0671; found: 323.0675.
3'-Amino-4-methoxy-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
carbonitrile (4c)
2-(1-([1,1'-Biphenyl]-4-yl)-3,3-bis(methylthio)allylidene)-
malononitrile (2q)
Brown solid; yield: 108 mg (55%); mp = 115–118 °C; IR (KBr): 3474,
2925, 2205, 1462-1599 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.39
(s,3H, -SMe), 3.87 (s, 3H, -OMe), 4.25 (s, 2H, NH2), 6.63 (s, 1H, ArH),
7.03 (d, J = 12 Hz, 2H, ArH), 7.53 (dd, J = 1.2 Hz, J = 8.4 Hz, 4H, ArH),
8.40 (d, J = 8.8 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3): δ 15.2,
55.3, 92.5, 114.0, 114.1, 120.0, 124.2, 124.8, 129.7, 130.6, 130.8,
131.8, 141.8, 145.2, 147.0, 148.0, 160.2; HRMS (ESI): m/z [M + H]+
calcd for C21H18N3O3S: 392.1063; found: 392.1059.
Brown solid; yield: 3.20 g (92%); mp = 125–127 °C; IR (KBr):
1
2923, 2214, 1428-1603cm–1; H NMR (400 MHz, CDCl3): δ 2.30
(s,3H, -SMe), 2.60 (s, 3H, -SMe), 6.51 (s, 1H, ArH), 7.38 (t, J =
7.2 Hz, 1H,ArH), 7.42-7.47 (m, 4H, ArH), 7.64 (d, J = 8.8 Hz, 2H,
ArH), 7.69 (d, J = 8.4 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3): δ
16.7, 17.8, 77.7, 114.1, 114.2, 114.6, 127.2, 127.7, 128.2,
129.0, 129.3, 133.3, 139.7, 144.2, 165.0, 167.7; HRMS (ESI):
m/z [M + H]+ calcd for C20H17N2S2: 349.0828; found: 349.0820.
2-(1-Cyclopropyl-3,3-bis(methylthio)allylidene)malononitrile
(2r)
Brown liquid; yield: 1.42 g (60%); mp = 40-42 °C; IR (KBr):
2924, 2217, 1426-1512 cm–1; 1H NMR (400 MHz, CDCl3): δ
0.93-0.97 (m,2H), 1.23-1.28 (m, 3H), 2.42 (s,3H, -SMe), 2.51 (s,
3H, -SMe), 5.73 (s, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ 10.4,
11.2, 16.4, 17.3, 18.5, 82.5, 113.4, 113.5, 114.1, 154.3, 177.0;
HRMS (ESI): m/z [M + H]+ calcd for C11H13N2S2: 237.0515;
found: 237.0510.
3'-Amino-3,4-dimethoxy-5'-(methylthio)-4''-nitro-[1,1':4',1''-
terphenyl]-2'-carbonitrile (4d)
Brown solid; yield: 117 mg (53%); mp = 113–115 °C; IR (KBr): 3408,
2925, 2215, 1435-1568 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.40
(s,3H, -SMe), 3.94 (s, 3H, -OMe), 3.96 (s, 3H, -OMe), 4.27 (s, 2H, -
NH2), 6.56 (s, 1H, ArH), 6.99 (d, J = 8.4 Hz, 1H, ArH), 7.12-7.16 (m,
2H, ArH), 7.52 (d, J = 8.4 Hz, 2H, ArH), 8.39 (d, J = 8.0 Hz, 2H, ArH);
13C NMR (100 MHz, CDCl3): δ 15.3, 56.0, 56.1, 92.7, 111.3, 111.8,
114.1, 117.7, 120.2, 121.1, 125.0, 132.0, 132.0, 142.0, 145.3, 146.0,
147.0, 148.1, 149.0, 149.8; HRMS (ESI): m/z [M + H]+ calcd for
C22H20N3O4S: 422.1169; found: 422.1178.
General procedure for the synthesis of 3'-amino-5'-
(methylthio)-4''-nitro-[1,1':4',1''-teraryl]-2'-carbonitriles 4a-n:
A mixture of 2-(3,3-bis(methylthio)-1-arylallylidene)malono
nitriles 2 (0.5 mmol), 2-substituted-1-methyl-4-nitrobenzenes3
(0.5 mmol) and KOH (1.0 mmol) in DMF (4.0 mL) was stirred at
o
3'-Amino-2-methoxy-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
carbonitrile (4e)
60 C for 5 hours. When reaction was completed (monitored
by TLC), the crude mixture was poured onto the ice-water with
constant stirring. The mixture was then neutralized with 10%
HCl. The resulting precipitate was collected by filtration,
washed with water and dried. The crude was purified by silica
gel column chromatography (hexane/ethylacetate: 85/15) to
afford the desired products.
Brown solid; yield: 117 mg (42%); mp = 113–115 °C; IR (KBr): 3408,
2925, 2215, 1435-1568 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.36
(s,3H, -SMe), 3.90 (s, 3H, -OMe), 4.19 (s, 2H, -NH2), 6.63 (s, 1H, ArH),
7.04-7.09 (m, 2H, ArH), 7.30 (dd, J = 1.6 Hz, J = 7.2 Hz, 1H, ArH), 7.44
(td, J = 2.0 Hz, J = 8.4 Hz, 1H, ArH), 7.55 (d, J = 11.2 Hz, 2H, ArH),
8.40 (d, J = 8.8 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3): δ 15.3,
55.7, 94.8, 111.4, 115.2, 117.3, 120.5, 121.0, 125.0, 127.5, 130.5,
130.7, 132.0, 142.0, 143.1, 145.0, 146.3, 148.1, 156.5; HRMS (ESI):
m/z [M + H]+ calcd for C21H18N3O3S: 392.1063; found: 392.1062.
3'-Amino-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
carbonitrile (4a)
Brown solid; yield: 110 mg (60%); mp = 145–148 °C; IR (KBr): 3408,
2925, 2215, 1431-1568 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.39
(s,3H, -SMe), 4.27 (s, 2H, -NH2), 6.66 (s, 1H, ArH), 7.47-7.55 (m, 5H,
ArH), 7.57 (d, J = 8 Hz, 2H, ArH), 8.39 (d, J = 8.4 Hz, 2H, ArH); 13C
NMR (100 MHz, CDCl3): δ 14.01, 92.1, 114.2, 118.1, 121.7, 124.4,
127.3, 129.3, 131.6, 135.2, 138.7, 141.0, 143.1, 145.1, 147.6, 149.0;
3'-Amino-4-fluoro-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
carbonitrile (4f)
Brown solid; yield: 95 mg (50%); mp = 230–233 °C; IR (KBr): 3460,
1
2924, 2208, 1429-1597 cm–1; H NMR (400 MHz, CDCl3): δ 2.39 (s,
3H, -SMe), 4.27 (s, 2H, -NH2), 6.61 (s, 1H, ArH), 7.19 (t, J = 8.4 Hz,
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2H, ArH), 7.52-7.58 (m, 4H, ArH), 8.40 (dd, J = 2 Hz, J = 6.8 Hz, 2H, Brown solid; yield: 103 mg (47%); mp = 80–82 °C; IR (KBr): 3478,
View Article Online
–1
1
ArH); 13C NMR (100 MHz, CDCl3): δ14.3, 92.3, 115.7 (d, JC-F = 20 Hz), 2924, 2207, 1435-1569 cm ; H NMR (400 MHz, CDCl3): δ 2.41 (s,
118.0, 121.2, 124.0, 125.0, 128.6, 129.0 (d, JC-F = 60 Hz), 132.0, 3H, -SMe), 4.29 (s, 2H, NH2), 6.71 (s, 1H, ArH), 7.40 (d, J = 8 Hz, 1H,
138.2, 141.0, 145.0, 146.1, 147.0, 163.2 (d, JC-F = 270 Hz);HRMS ArH), 7.48 (t, J = 8.4 Hz, 2H, ArH), 7.55 (d, J = 8 Hz, 2H, ArH), 7.62-
(ESI): m/z [M + H]+ calcd for C20H15FN3O2S2: 380.0864; found: 7.74 (m, 6H, ArH), 8.41 (d, 2H, ArH); 13C NMR (100 MHz, CDCl3): δ
DOI: 10.1039/D0OB00998A
380.0870.
15.2, 92.4, 114.1, 117.4, 120.4, 124.8, 127.1, 127.3, 127.4, 127.5,
127.6, 128.8, 131.7, 137.3, 140.2, 141.7, 141.8, 145.5, 147.0, 148.8;
HRMS (ESI): m/z [M + H]+ calcd for C26H20N3O2S: 438.1271; found:
438.1270.
3'-Amino-4-chloro-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
carbonitrile (4g)
Brown solid; yield: 100 mg (50%); mp = 110–112 °C; IR (KBr): 3480,
2924, 2209, 1426-1521 cm–1; H NMR (400 MHz, CDCl3): δ 2.38 (s, 3'-Amino-2''-chloro-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
1
3H, -SMe), 4.27 (s, 2H, -NH2), 6.60 (s, 1H, ArH), 7.45-7.50 (m, 2H, carbonitrie (4l)
ArH), 7.50-7.58 (m, 4H, ArH), 8.39 (d, J = 8.0 Hz, 2H, ArH); 13C NMR Brown solid; yield: 82 mg (41%); mp = 188–190 °C; IR (KBr): 3462,
1
(100 MHz, CDCl3): δ15.3, 92.1, 114.1, 117.2, 120.0, 125.0, 125.6, 2924, 2211, 1430-1573 cm–1; H NMR (400 MHz, CDCl3): δ 2.42 (s,
128.0, 129.8, 131.8, 135.2, 137.0, 141.6, 144.8, 147.1, 148.2; HRMS 3H, -SMe), 4.24 (s, 2H, -NH2), 6.68 (s, 1H, ArH), 7.47-7.54 (m, 4H,
(ESI): m/z [M + H]+ calcd for C20H15ClN3O2S: 396.0568; found: ArH), 7.60 (d, J = 7.2 Hz, 2H, ArH), 8.29 (dd, J = 2.4 Hz, J = 8.4 Hz, 1H,
396.0580.
ArH), 8.48 (d, J = 2.4 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ
15.2, 93.0, 114.5, 117.3, 118.3, 123.0, 125.8, 128.5, 128.7, 129.0,
133.6, 136.5, 138.5, 140.4, 145.5, 146.6, 147.0, 149.0; HRMS (ESI):
m/z [M + H]+ calcd for C20H15ClN3O2S: 396.0568; found: 396.0573.
3'-Amino-4-bromo-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
carbonitrile (4h)
Brown solid; yield: 115 mg (52%); mp = 101–103 °C; IR (KBr): 3479,
2924, 2205, 1424-1571 cm–1; H NMR (400 MHz, CDCl3): δ 2.13 (s, 3'-Amino-2''-bromo-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
1
3H, -SMe), 4.04 (s, 2H, -NH2), 6.35 (s, 1H, ArH), 7.00 (d, J = 1.2 Hz, carbonitrile (4m)
2H, ArH), 7.19 (d, J = 8.4 Hz, 2H, ArH), 7.37 (d, J = 14 Hz, 2H, ArH), Brown solid; yield: 88 mg (40%); mp = 170–172 °C; IR (KBr): 3369,
1
8.14 (d, J = 8 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3): δ 15.2, 92.3, 2925, 2208, 1459-1572 cm–1; H NMR (400 MHz, CDCl3): δ 2.42 (s,
114.0, 117.2, 120.7, 123.4, 125.0, 130.0, 131.7, 132.0, 137.3, 141.5, 3H, -SMe), 4.21 (s, 2H, -NH2), 6.68 (s, 1H, ArH), 7.47-7.53 (m, 4H,
144.7, 145.6, 147.0, 148.1; HRMS (ESI): m/z [M + H]+ calcd for ArH), 7.61 (dd, J = 1.2 Hz, J = 8.4 Hz, 2H, ArH), 8.34 (dd, J = 2.4 Hz, J
C20H15BrN3O2S2: 440.0063; found: 440.0060.
= 8.0 Hz, 1H, ArH), 8.65 (d, J = 1.6 Hz, 1H, ArH); 13C NMR (100 MHz,
CDCl3): δ 15.1, 92.7, 114.3, 117.2, 120.0, 123.5, 126.0, 128.5, 128.7,
129.0, 129.0, 133.4, 138.3, 142.5, 145.3, 146.4, 146.6, 148.5; HRMS
(ESI): m/z [M + H]+ calcd for C20H15BrN3O2S: 440.0063; found:
442.0055.
3'-Amino-3-bromo-5'-(methylthio)-4''-nitro-[1,1':4',1''-terphenyl]-2'-
carbonitrile (4i)
Brown solid; yield: 107 mg (48%); mp = 185–187 °C; IR (KBr): 3474,
1
2925, 2207, 1427-1567 cm–1; H NMR (400 MHz, CDCl3): δ 2.40 (s,
3H, -SMe), 4.29 (s, 2H, -NH2), 6.61 (s, 1H, ArH), 7.38 (t, J = 8 Hz, 1H, 3'-Amino-2''-bromo-4-methyl-5'-(methylthio)-4''-nitro-[1,1':4',1''-
ArH), 7.53 (d, J = 8.4 Hz, 3H, ArH), 7.59-7.61 (m, 1H, ArH), 7.68-7.69 terphenyl]-2'- carbonitrile (4n)
(m, 1H, ArH), 8.41 (d, J = 8.0 Hz, 2H, ArH); 13C NMR (100 MHz, Brown solid; yield: 95 mg (42%); mp = 200–202 °C; IR (KBr): 3468,
1
CDCl3): δ 14.0, 92.1, 117.6, 118.1, 120.0, 122.0, 124.4, 127.3, 128.7, 2925, 2215, 1435-1568 cm–1; H NMR (400 MHz, CDCl3): δ 2.41 (s,
129.3, 131.6, 134.7, 138.7, 141.0, 143.1, 145.1, 147.6, 149.0; HRMS 3H, -SMe), 2.43 (s, 3H, -CH3), 4.19 (s, 2H, -NH2), 6.67 (s, 1H, ArH),
(ESI): m/z [M + H]+ calcd for C20H15BrN3O2S2: 440.0063; found: 7.31 (d, J = 8.0 Hz, 2H, ArH), 7.50 (d, J = 8.4 Hz, 3H, ArH), 8.33 (dd, J
440.0068.
= 2.4 Hz, J = 8.4 Hz, 1H, ArH), 8.65 (d, J = 6.0 Hz, 1H, ArH); 13C NMR
(100 MHz, CDCl3): δ 15.2, 21.4 92.8, 114.3, 117.5, 120.0, 123.6,
126.1, 128.4, 129.0, 129.5, 133.5, 135.6, 139.1, 145.2, 145.2, 146.6,
146.7, 148.6; HRMS (ESI): m/z [M + H]+ calcd for C21H17BrN3O2S:
454.0219; found: 454.0223.
2-Amino-6-(methylthio)-4-(naphthalen-2-yl)-4'-nitro-[1,1'-biphenyl]-3-
carbonitrile (4j)
Brown solid; yield: 98 mg (45%); mp = 180–183 °C; IR (KBr): 3470,
2925, 2215, 1435-1568 cm–1; H NMR (400 MHz, CDCl3): δ 2.32 (s,
1
3H, -SMe), 4.30 (s, 2H, -NH2), 6.71 (s, 1H, ArH), 7.49-7.55 (m, 3H, Synthesis of 3-amino-2-aryl-5-(methylthio)-[1,1'-biphenyl]-4-
ArH), 7.56-7.62 (m, 3H, ArH), 7.76 (d, J = 8 Hz, 1H, ArH), 7.95 (t, J = carbonitriles 6a-k: A mixture of 2-(3,3-bis(methylthio)-1-
6.8 Hz, 2H, ArH), 8.42-8.46 (m, 2H, ArH); 13C NMR (100 MHz, CDCl3): arylallylidene)malononitrile 2 (0.5 mmol), nitroethane 5 (0.5
δ 15.1, 95.0, 115.7, 120.6, 125.0, 125.1, 125.3, 126.1, 126.6, 127.1, mmol), and KOH (1.0 mmol) in DMF (4.0 mL) was stirred at 40-
o
128.5, 129.2, 131.3, 131.7, 131.8, 133.6, 136.1, 141.7, 144.8, 145.0, 45 Cfor 1 hour. After the completion, the reaction mixture
146.5, 148.1; HRMS (ESI): m/z [M + NH4]+ calcd for C24H21N4O2S: was poured onto crushed ice with vigorous stirring followed by
429.1385; found: 429.1380.
neutralization with 10% hydrochloric acid. The precipitate
obtained was filtered, washed with H2O and dried. The crude
was purified by silica gel column chromatography using
3''-Amino-5''-(methylthio)-4'''-nitro-[1,1':4',1'':4'',1'''-quaterphenyl]-2''-
carbonitrile (4k)
8 | J. Name., 2012, 00, 1-3
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ARTICLE
hexane/ethylacetate (90:10) as an eluent to afford biaryl 130.1, 130.8, 140.2, 144.6, 147.2, 156.6; HRMS (ESI): m/z [M +
View Article Online
+
DOI: 10.1039/D0OB00998A
product.
H] calcd for C16H17N2OS: 285.1056; found: 285.1049.
3-Amino-4-methyl-5-(methylthio)-[1,1'-biphenyl]-2-carbonitrile
(6a)
3-Amino-4'-fluoro-4-methyl-5-(methylthio)-[1,1'-biphenyl]-2-
carbonitrile (6f)
White solid; yield: 90 mg (70%); mp = 80–82 °C; IR (KBr): 3483, White solid; yield: 71 mg (52%);mp = 188–190 °C; IR (KBr): 3473,
3383, 2923, 2854, 2216, 1734, 1441-1628 cm–1; 1H NMR (400 MHz, 3378, 2922, 2211, 1739, 1424-1696 cm–1; 1H NMR (400 MHz,
CDCl3): δ 2.20 (s, 3H, -SMe), 2.48 (s, 3H, -CH3), 4.49 (s, 2H, -NH2), CDCl3): δ 2.19 (s, 3H, -CH3), 2.48 (s, 3H, -SMe), 4.51 (s, 2H, -NH2),
6.60 (s, 1H, ArH), 7.40-7.48 (m, 3H, ArH), 7.51-7.52 (m, 1H, ArH), 6.55 (s, 1H, ArH), 7.14 (t, J = 8.4 Hz,2H, ArH), 7.49 (dd, J = 5.6 Hz, J =
7.53-7.54 (m, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ 13.3, 15.3, 8.8 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3): δ 13.1, 15.2, 92.1,
92.3, 114.6, 117.1, 118.1, 128.5, 128.6, 128.6, 139.0, 143.3, 145.0, 114.4, 115.6 (d, JC-F = 32 Hz), 117.1, 118.0, 130.1 (d, JC-F = 10 Hz),
148.0; HRMS (ESI): m/z [M + H]+calcd for C15H15N2S: 255.0950; 135.0, 142.1, 145.0, 147.8, 162.8 (d, JC-F = 248.8 Hz); HRMS (ESI):
found: 255.0942.
m/z [M + H]+calcd for C15H14FN2S: 273.0856; found: 273.0848.
3-Amino-4,4'-dimethyl-5-(methylthio)-[1,1'-biphenyl]-2-
carbonitrile (6b)
3-Amino-2',4'-dichloro-4-methyl-5-(methylthio)-[1,1'-biphenyl]-2-
carbonitrile (6g)
White solid; yield: 97 mg (72%); mp = 93–95 °C; IR (KBr): 3476, White solid; yield: 81 mg (50%); mp = 165–167 °C; IR (KBr): 3480, 3383,
3381, 2923, 2208, 1703, 1427-1628 cm–1; 1H NMR (400 MHz, 2924, 2212, 1737, 1455-1630 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.20 (s,
CDCl3): δ 2.12 (s, 3H, -CH3), 2.33 (s, 3H, -SMe), 2.40 (s, 3H, -CH3), 3H, -CH3), 2.45 (s, 3H, -SMe), 4.48 (s, 2H, -NH2), 6.49 (s, 1H, ArH), 7.28
4.41 (s, 2H, -NH2), 6.51 (s, 1H, ArH), 7.19 (d, J = 9.2 Hz,2H, ArH), 7.35 (s,1H, ArH), 7.33 (dd, J = 2.4 Hz, J = 8.4 Hz, 1H, ArH), 7.52 (d, J = 1.6 Hz,1H,
(d, J = 8.4 Hz,2H, ArH); 13C NMR (100 MHz, CDCl3): δ 13.1, 15.2, ArH); 13C NMR (100 MHz, CDCl3): δ 13.3, 15.3, 93.5, 115.1, 117.1, 118.0,
21.2, 92.2, 114.4, 116.7, 118.1, 128.3, 129.2, 136.0, 138.4, 143.2, 127.3, 128.3, 129.8, 132.0, 135.2, 136.2, 139.5, 145.0, 147.7; HRMS (ESI):
144.7, 147.7; HRMS (ESI): m/z [M + H]+calcd for C16H17N2S: m/z [M + H]+calcd for C15H13Cl2N2S: 323.0171; found: 323.0158.
269.1107; found: 269.1099.
3-Amino-4'-bromo-4-methyl-5-(methylthio)-[1,1'-biphenyl]-2-
3-Amino-4'-methoxy-4-methyl-5-(methylthio)-[1,1'-biphenyl]-2-
carbonitrile (6c)
carbonitrile (6h)
White solid; yield: 92 mg (55%);mp = 175–177 °C; IR (KBr): 3468,
White solid; yield: 93 mg (65%);mp = 95–97 °C; IR (KBr): 3461, 3374, 3375, 2923, 2854, 2209, 1712, 1461-1637 cm–1; H NMR (400 MHz,
2924, 2207, 1731, 1459-1635 cm–1; 1H NMR (400 MHz, CDCl3): δ CDCl3): δ 2.20 (s, 3H, -CH3), 2.48 (s, 3H, -SMe), 4.50 (s, 2H, -NH2),
2.19 (s, 3H, -CH3), 2.48 (s, 3H, -SMe), 3.85 (s, 3H, -OMe), 4.48 (s, 2H, 6.55 (s, 1H, ArH), 7.41-7.47 (m,4H, ArH); 13C NMR (100 MHz, CDCl3):
-NH2), 6.57 (s, 1H, ArH), 6.99 (d, J = 8.8 Hz,2H, ArH), 7.47 (d, J = 8.4 δ 13.3, 15.3, 92.0, 114.4, 117.4, 118.0, 129.0, 130.0, 134.7, 137.7,
Hz,2H, ArH); 13C NMR (100 MHz, CDCl3): δ 13.1, 15.2, 55.3, 92.1, 142.0, 145.2, 148.0; HRMS (ESI): m/z [M + H]+calcd for C15H14BrN2S:
114.0, 114.3, 116.5, 118.2, 129.6, 131.3, 143.0, 144.7, 147.7, 159.8; 333.0056; found: 333.0067.
1
HRMS (ESI): m/z [M + H]+calcd for C16H17N2OS: 285.1056; found:
3-Amino-3'-bromo-4-methyl-5-(methylthio)-[1,1'-biphenyl]-2-
carbonitrile (6i)
285.1049.
3-Amino-3',4'-dimethoxy-4-methyl-5-(methylthio)-[1,1'-biphenyl]-2-
carbonitrile (6d)
White solid; yield: 82 mg (49%);mp = 180–185 °C; IR (KBr): 3376,
2921, 2206, 1703, 1445-1637 cm–1; 1H NMR (400 MHz, CDCl3): δ
White solid; yield: 76 mg (48%); mp = 120–122 °C; IR (KBr): 3468, 2.20 (s, 3H, -CH3), 2.49 (s, 3H, -SMe), 4.52 (s, 2H, -NH2), 6.55 (s, 1H,
1
3381, 2924, 2852, 2206, 1708, 1442-1708 cm–1; H NMR (400 MHz, ArH), 7.33 (t, J = 8.0 Hz, 1H, ArH), 7.45-7.48 (m, 1H, ArH), 7.53-7.56
CDCl3): δ 2.19 (s, 3H, -CH3), 2.48 (s, 3H, -SMe), 3.92-3.93 (s, 6H, - (m,1H, ArH), 7.63 (t, J = 2.0 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3):
OMe), 4.49 (s, 2H, -NH2), 6.59 (s, 1H, ArH), 6.95 (d, J = 8.0 Hz,1H, δ 13.3, 15.4, 92.1, 114.5, 117.7, 122.6, 122.7, 127.4, 130.1, 131.5,
ArH), 7.06-7.09 (m,2H, ArH); 13C NMR (100 MHz, CDCl3): δ 13.2, 131.6, 141.0, 141.6, 145.2, 148.0; HRMS (ESI): m/z [M + H]+calcd for
15.4, 56.0, 56.1, 92.3, 111.2, 112.0, 114.5, 116.8, 118.3, 121.1, C15H14BrN2S: 333.0056; found: 333.0047.
131.7, 143.1, 144.8, 148.0, 148.8, 149.4; HRMS (ESI): m/z [M +
H]+calcd for C17H19N2O2S: 315.1162; found: 315.1155.
2-Amino-3-methyl-4-(methylthio)-6-(naphthalen-2-yl)benzonitrile
(6j)
3-Amino-2'-methoxy-4-methyl-5-(methylthio)-[1,1'-biphenyl]-2-
carbonitrile (6e)
White solid; yield: 93 mg (61%); mp = 167–169 °C; IR (KBr): 3486,
White solid; yield: 70 mg (49%); mp = 95–93 °C; IR (KBr): 3461, 3376, 2924, 2208, 1705, 1436-1629 cm–1; 1H NMR (400 MHz,
3374, 2924, 2207, 1731, 1459-1635 cm–1; 1H NMR (400 MHz, CDCl3): δ 2.22 (s, 3H, -CH3), 2.50 (s, 3H, -SMe), 4.53 (s, 2H, -NH2),
CDCl3): δ 2.19 (s, 3H, -CH3), 2.45 (s, 3H, -SMe), 3.84 (s, 3H, -OMe), 6.70 (s, 1H, ArH), 7.51-7.53 (m,2H, ArH), 7.64 (dd, J = 1.6 Hz, J = 8.4
4.42 (s, 2H, -NH2), 6.56 (s, 1H, ArH), 7.00-7.05 (m,2H, ArH), 7.23 Hz, 1H, ArH), 7.86-7.95 (m, 3H, ArH), 8.00 (s, 1H, ArH); 13C NMR
(m,1H, ArH), 7.37-7.41 (m,1H, ArH); 13C NMR (100 MHz, CDCl3): δ (100 MHz, CDCl3): δ 13.3, 15.4, 92.5, 115.0, 117.2, 118.2, 126.4,
13.3, 15.3, 55.6, 94.3, 111.3, 115.4, 117.2, 118.0, 120.7, 128.0, 126.5, 126.6, 127.8, 128.4, 133.1, 133.2, 136.4, 143.3, 145.0, 148.0;
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
HRMS (ESI): m/z [M + H]+calcd for C19H17N2S: 305.1107; found:
305.1104.
6
(a) P. Ling and Q. Liu, Synlett. 2011, 1073–1080; (b) K.
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Peseke. J. Prakt. Chem., 1981, 323, 499; (c) K. Peseke,
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Zeitschrift Für Chemie, 1977, 17, 288.
7
(a) J. Hassan, M. Sevignon, C. Gozzi, E. Chulz and M. Lemaire,
Chem. Rev. 2002, 102, 1359–1469; (b) A. F. Littke, C. Dai and
G. C. Fu, J. Am. Chem. Soc.2000, 122, 4020–4028; (c) A. J.
Blake, P. A. Cooke, K. J. Doyle, S. Gair and N. S. Simpkins,
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and R. Pratap, SynOpen. 2018, 2, 276–284.
3-Amino-4-methyl-5-(methylthio)-[1,1':4',1''-terphenyl]-2-
carbonitrile (6k)
White solid; yield: 103 mg (62%); mp = 90–92 °C; IR (KBr): 3382,
3376, 2925, 2208, 1705, 1462-1629 cm–1; 1H NMR (400 MHz,
CDCl3): δ 2.21 (s, 3H, -CH3), 2.50 (s, 3H, -SMe), 4.53 (s, 2H, -NH2),
6.65 (s, 1H, ArH), 7.37 (t, J = 7.2 Hz,1H, ArH), 7.47 (t, J = 7.6 Hz,2H,
ArH), 7.59-7.63 (t, J = 8.8 Hz, 4H, ArH), 7.69 (d, J = 8.4 Hz, 2H, ArH);
13C NMR (100 MHz, CDCl3): δ 13.3, 15.4, 92.2, 114.6, 117.2, 118.2,
127.2, 127.4, 127.6, 129.0, 129.0, 138.0, 140.5, 141.4, 142.8, 145.0,
148.0; HRMS (ESI): m/z [M + H]+calcd for C21H19N2S: 331.1263;
found: 331.1247.
8
9
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Conflicts of interest
There are no conflicts of interest to declare.
Acknowledgements
We are grateful to acknowledge Indian Council of Medical
Research (ICMR), New Delhi for financial support. RP is
thankful to the University of Delhi for providing instrument
facilities to accomplish this work. S. is thankful to UGC, New
Delhi for providing research fellowship.
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