α-Aroylidineketene dithioacetal chemistry: CuI catalyzed synthesis of 2-styryl benzimidazoles enroute to regioselective hydrothiolation

Article abstract of DOI:10.1016/j.tet.2015.06.008

Abstract Reactivity of α-aroylidineketene dithioacetals 2 was investigated to synthesize novel 2-styrylbenzimidazole derivatives 4 and their hydrothiolated product 2-(2-(methylthio)-2-arylethyl)-1H-benzo[d]imidazoles 5 has been reported. Compounds 4 and 5

Full text of DOI:10.1016/j.tet.2015.06.008

Accepted Manuscript
α-Aroylidineketene Dithioacetal Chemistry: CuI Catalyzed Synthesis of 2-Styryl
benzimidazoles Enroute to Regioselective Hydrothiolation
Pandi Dhanalakshmi, Sivakumar Shanmugam
PII:
S0040-4020(15)00863-7
10.1016/j.tet.2015.06.008
TET 26843
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 5 February 2015
Revised Date: 1 June 2015
Accepted Date: 2 June 2015
Please cite this article as: Dhanalakshmi P, Shanmugam S, α-Aroylidineketene Dithioacetal Chemistry:
CuI Catalyzed Synthesis of 2-Styryl benzimidazoles Enroute to Regioselective Hydrothiolation,
Tetrahedron (2015), doi: 10.1016/j.tet.2015.06.008.
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ACCEPTED MANUSCRIPT
Graphical Abstract
α-Aroylidineketene Dithioacetal Chemistry: CuI Catalyzed Synthesis of 2-
Styryl benzimidazoles Enroute to Regioselective Hydrothiolation
∗
Pandi Dhanalakshmi and Sivakumar Shanmugam
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University,
Madurai – 625021, Tamil Nadu, India

ACCEPTED MANUSCRIPT
α-Aroylidineketene Dithioacetal Chemistry: CuI Catalyzed Synthesis of 2-
Styryl benzimidazoles Enroute to Regioselective Hydrothiolation
∗
Pandi Dhanalakshmi and Sivakumar Shanmugam
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University,
Madurai – 625021, Tamil Nadu, India
Abstract: Reactivity of α-aroylidineketene dithioacetals 2 was investigated to synthesize
novel 2-styrylbenzimidazole derivatives 4 and their hydrothiolated product 2-(2-(methylthio)-
2
-arylethyl)-1H-benzo[d]imidazoles 5 has been reported. Compound 4 and 5 were
synthesized by cyclocondensation of α-aroylidineketene dithioacetals 2 and o-phenylene
diamine (OPD) 3 in the presence and absence of copper catalyst. Regioselective one-pot
tandem hydrothiolation of olefin functionality in 4 was achieved under AcOH conditions.
1
.
Introduction
1
Functionalized ketene dithioacetals are readily accessible versatile synthons and their
2
chemistry has received considerable attention for several years. α-aroylidineketene
dithioacetals and related compounds with the basic structural unit Z-CH=C(SR) possess a
2
push pull alkene functionality accompanied with both nucleophilic and electrophilic
characters (Z=COAr, COCH=CHAr etc). This complementary electronic nature of the
1
-2
functionalized ketene dithioacetals has been utilized in the assembly of novel heterocycles.
3
Recently, we reported, the synthesis of 2-arylbenzimidazole by cyclocondensation of α-
4
aroylketene dithioacetals (AKDTA) with OPD 3 under AcOH (cat.)/H O media. On this
2
account, we got interested to examine the reactivity of α-aroylidineketene dithioacetal 2 by
treating with 3 under similar cyclocondensation conditions. Interestingly, compound 4 was
Keywords: α-aroylidineketene dithioacetals; 2-styryl benzimidazole; o-phenylene diamine;
regioselective hydrothiolation; copper iodide; acetic acid
∗
Corresponding author: e-mail: shivazzen@mkuniversity.org
2

ACCEPTED MANUSCRIPT
obtained as major along with a 25% of byproduct, which has been identified as
hydrothiolated product of 4. Hydrothiolation across the C=C bond is a key transformation of
5
significant interest in organic chemistry. It constitutes a key role in biochemical synthesis of
6
biologically active compounds. A large number of bioactive organo-sulphur compounds are
known as valuable feedstock chemicals finding utility as synthetic intermediates and
7
functional materials.
On the other hand, benzimidazoles are important class of compounds that found
8
9
significant interest in contemporary organic synthesis , and medicinal chemistry. A series of
cyano and amino substituted derivatives of 2-styryl benzimidazoles and benzimidazo[1,2-
α]quinolines have been evaluated for their biological activity in DNA and RNA binding
9
ability . Currently, only few reports are available in the literature for the synthesis of 2-styryl
benzimidazoles. Most of the previous syntheses of 2-styryl benzimidazoles involved the
condensation of 1,2-phenylenediamine with either cinnamaldehyde in the presence of
1
0
11
12
13
Yb(OTf)3 TiCl4 FePO4 and KI/DMF-H O or cinnamic acid under relatively harsh
,
,
,
2
1
4
15
16
17
condition such as PPA , ethylene glycol , glycerol , 4N HCl and H SO -ethylene
2
4
1
8
glycol. Another related method by Okumara et al. included condensation of 1,2-
19
phenylenediamine with cinnamoyl chloride in toluene under reflux conditions. Alternative
methods of 2-styryl benzimidazole synthesis includes steps such as Philips condensation
followed by reaction of the 2-methyl benzimidazole intermediate with various aromatic
2
0
21
aldehydes; reactions of α,β, unsaturated ester with AlMe -Toluene under reflux conditions
3
1
(
24h); and oxidative C-N coupling reaction of N -Benzyl (substituted benzene)-1,2-diamines
2
2
using TEMPO as oxidant. However, none of the classical methods exhibited broad substrate
scope and utilized milder reaction conditions. Here in for the first time we report the
synthesis of 2-styryl benzimidazoles from α-aroylidineketene dithioacetals under milder
reaction conditions.
Besides, substituted benzimidazoles incorporated with alkyl/aryl sulfide functionalities are
known to possess high anthelmintic activity against intestinal nematodes in human as well as
23,24
in animals.
which are key synthetic intermediates
there are few reports on hydrothiolation of α,β-unsaturated carbonyl compounds using
Additionally, the sulfides could be useful synthons for preparation of sulfones
2
3,24
23-25
and potential bioactive compounds.
Although,
2
6,27
various catalysts
to the best of our knowledge there are no reports on hydrothiolation of
olefin functionality as in compound 4. In the present work, the different reactivity of α-
3

ACCEPTED MANUSCRIPT
aroylidineketene dithioacetals 2 compared to α-aroylketene dithioacetals were exploited
which led to unprecedented formation of 5 besides the expected product 4. This finding gave
us scope to diverge from this point and establish methodologies for selective synthesis of 2-
styryl benzimidazoles 4 and regioselective hydrothiolation product 5.
2
. Results and discussion
The selected substrates 2a-y were prepared by aldol condensation of 4,4-
bis(methylthio)but-3-en-2-one 1 with various aryl aldehydes under basic conditions (Table 1,
2
8
see SI). At the onset of our studies, the cyclocondensation of readily prepared 2a and 3 in
o
the presence of acetic acid (50 mol%) in water at 100 C was investigated. We observed that
the expected product 2-styryl benzimidazole 4a was obtained only 50% yield along with a
by-product that formed in 25% yield (Scheme 1). The by-product was identified as 2-(2-
(methylthio)-2-arylethyl)-1H-benzo[d]imidazole 5a which resulted from regioselective
1
13
hydrothiolation of 4a. Compounds 4a&5a were confirmed by H& C NMR spectrum.
Scheme 1. Reaction of α-aroylidineketene dithioacetal 2a and OPD 3 in the presence of
AcOH (cat)
In order to modulate the selective synthesis of 4a, several reaction conditions using
various metal catalysts in AcOH/H O media were explored (Table 1). Interestingly, in the
2
presence of copper iodide (CuI, 5 mol%) the cyclocondensation of 2a and 3 in AcOH/water
(Table 1, entry 1) led to isolation of compound 4a in 89% yield. When the same reaction was
conducted under microwave conditions, 4a was isolated in 87% yield (Table 1, entry 2).
Further, the formation of 4a increased to 92% yield by increasing the amount (10 mol%) of
copper iodide (Table 1, entry 3). Additionally, when other copper salts such as CuBr or
Cu(OTf) were employed instead of copper iodide, the yields of 4a was reduced to 75 & 87%
2
(
Table 1, entries 6-7). On the other hand, when ZnCl was used as catalyst, compounds 4a
2
was obtained in 59% yield along with 35% of 5a (Table 1, entry 8). In addition to Cu
4

ACCEPTED MANUSCRIPT
catalysts, the cyclocondensation was explored using other metal catalysts such as Yb(OTf)3,
Ag(OTf), and In(OTf) to afford 4a in 84-89% yields (Table 1, entries 9-12).
3
Table 1. Optimization of the selective synthesis of 2-styrylbenzimidazole 4a in one-pot
cyclocondensation between 2a & 3
Entry Solvent Catalyst
Temp. Time
Yield (%)
89
o
(
C)
(min)
180
5
1
2
3
4
5
6
7
8
9
1
1
1
1
H O
CuI/AcOH (5/50)
CuI/AcOH (5/50)
CuI/AcOH (10/50)
100
100
100
70
2
a,c
H O
2
87
H O
2
180
120
18
92
MeCN CuI/AcOH (10/50)
85
c,d
H O
2
CuI (10)
100
100
70
-
b
DMF
CuBr (10)
210
180
180
180
180
150
180
180
75
b
MeCN Cu(OTf) (10)
87
2
b
EtOH
ZnCl (20)
90
59
2
b
MeCN Yb(OTf) (10)
70
84
3
b
0
1
2
3
DMF
Yb(OTf) (10)
100
70
86
3
b
MeCN Ag(OTf) (10)
89
b
MeCN In(OTf) (10)
70
86
3
d
MeCN InCl (10)
70
--
3
a
b
trace of 2-methyl benzimidazole was isolated.; minor amount of unreacted 2 was recovered& these
c
d
reactions performed without acetic acid. Under microwave (MW), No reaction.
There was no improvement towards the yield of 4a even the catalysts were used in
stoichiometric amounts. Notably, in the absence of AcOH, the cyclocondensation and thereby
formation of 4a was not observed (Table 1, entry 5). The reason could be that AcOH in this
reaction is acting as a catalyst as well as co-solvent. Following the optimized conditions
(
AcOH and CuI in H O at 100 ºC for 3 h Table 1, entry 3), the cyclocondensation was
2
explored for synthesis of 4b-q (Table 2).
5

ACCEPTED MANUSCRIPT
Table 2. Synthesis of 2-styryl benzimidazoles 4a-q from cyclocondensation of 3 and wide
a
range of α- aroylidineketene dithioacetals 2a-q using the optimized conditions
O
H N
H
N
2
AcOH/CuI
Ar
°
H O, 100 C,
2
H N
2
Ar
N
MeS
a-q
SMe
1-3h, 72-92 %
2
3
4a-q
H
H
H
N
N
OMe
N
MeO
N
N
N
4a (92%)
4b (83%)
4c (80%)
H
N
H
H
N
Cl
N
MeO
N
N
Cl
N
4d (87%)
4e (85%)
4f (84%)
H
N
H
H
N
F
F
N
N
N
F
N
4g (89%)
4h (86%)
4i (87%)
H
N
H
N
H
N
Br
N
Br
F
N
NC
Cl
N
4j (85%)
4k (83%)
4l (88%)
H
N
H
H
N
F
N
Cl
O N
N
N
N
2
4m (89%)
4n (91%)
4o (90%)
H
H
N
OMe
N
Br
Br
N
F
N
4p (84%)
4q (82%)
a
Optimized Reaction conditions: 2 (1mol), 3 (1mol), 50 mol% AcOH, 10mol% CuI, Water (5mL), reflux,
1
00 ºC, 1-2.5 h. Isolated yields refer to 2.
6

ACCEPTED MANUSCRIPT
It was observed that variants of 2a incorporating substitution of phenyl rings with Cl, F, Br
and electron withdrawing as well as donating groups underwent cyclocondensation smoothly
2
9a
29b
in excellent yields (79-92%). The structure of 4g & 4n was confirmed on the basis of
single crystal x-ray (Figure. 1).
Figure 1. X-ray Crystal structures of 2-styryl benzimidazoles 4g & 4n
As a further variation of phenyl ring in 2a, we introduced polyaryls such as naphthalene,
anthracene & pyrene molecules and corresponding transformations were observed from 2s-u
to 4s-u in good yields (Scheme 2).
7

ACCEPTED MANUSCRIPT
O
H
N
i
N
MeS
SMe
2s
4s (80%)
H
N
O
i
N
MeS
SMe
2t
4t (79%)
O
H
N
i
N
MeS
SMe
4u (81%)
2
u
Reaction Condition: (i) 2 (1mol), 3 (1mol), 50 mol% AcOH, 10 mol% CuI, Water (5mL),
reflux, 100 ºC, 1-2.5 h. Isolated yields refer to 2.
Scheme 2. Substrate scope for the synthesis of 2-styryl benzimidazole 4s-u
Further, the cyclocondensation was extended to the heteroaryl substrates 2v-y which
resulted in synthesis of 4v-y in 82-89% yields (Table 3). Overall, inclusive cyclocondensation
of 2 and 3, in all these transformations, we did not find the formation 5 in the presence of
copper catalyst.
a
Table 3. Substrate scope in the synthesis of compounds 4v-y from reaction of 3 and α-
heteroaroylidineketene dithioacetals 2v-y
8

ACCEPTED MANUSCRIPT
(i) 2 (1mol), 3 (1mol), 50 mol% AcOH, 10 mol%, CuI, Water (5mL), reflux, 100 ºC, 1-2.5
h. Isolated yields refer to 2.
On the contrary, optimization of cyclocondensation reaction aimed at achieving selective
one-pot synthesis of 5a seemed a very challenging task. In this regard, we envisaged that
cyclocondensation 2a with OPD 3 in the presence of acetic acid initially results in formation
of compound 4a along with MeSH and further reaction of these two intermediates leads to
the formation of 5a. The formation of 5a was investigated by exploring several reaction
conditions.
Table 4. Optimization of the selective synthesis of 5a during one-pot tandem
hydrothiolation
Temp Time Yield
Entry Solvent Acid catalyst
o
(
C)
(min) (%)
a
1
2
3
4
H O
2
AcOH (50)
AcOH (50)
80
90
70
90
120
120
120
120
25
28
28
34
EtOH
MeCN AcOH (50)
EtOH AcOH (50)
9

ACCEPTED MANUSCRIPT
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
H O
p-TsOH (50)
L-Proline (50)
HCl (0.1M, 50)
AcOH (50)
AcOH (50)
AcOH (50)
p-TsOH (50)
HCl (0.1M)
HCOOH (50)
80
90
90
100
80
80
80
80
50
120
60
3
5
5
3
5
10
5
72 h
60
50
25
25
15 h
25
25
30
38
21
25
22
24
30
28
2
EtOH
EtOH
None
b
b
b
b
b
b
H O
2
0
1
2
3
4
5
6
7
8
9
0
H O
2
H O
2
H O
2
None
80
80
H O
H SO4 (0.1M)
2
2
a,c
None
None
None
None
None
None
AcOH (100)
AcOH (50)
AcOH (60)
AcOH (80)
AcOH (100)
AcOH (10Vol)
RT
100
100
100
100
110
-
30
40
40
45
75
a
products 5a accompanied with <10% of 2-methyl benzimidazole as a side product by the
b
c
reaction of AcOH and 3 under heating. Under microwave (MW) condition. Unreacted 2
was recovered.
An initial attempt towards the optimization includes the reaction of 2a and OPD 3 at 100
o
C in presence of catalytic amount of acetic acid (50 mol%) in ethanol/acetonitrile to afford
5
a in 28-34% yields (Table 4, entries 2-4). The similar cyclocondensation was performed
using other acid catalysts such as p-TsOH and L-proline, the yields of 5a formation did not
improve whereas in presence of HCl the yields increased up to 38% (Table 4, entries 5-7).
Further, the reactions were performed in water/EtOH with microwave irradiation at 80-100
o
C for 3-10 min in the presence of acid catalysts such as p-TsOH, HCl, HCOOH, sulphuric
acid to yield 5a with 21-38% yield (Table 4, entries 8-14). The hydrothiolation product 5a
was not observed when the reaction was performed in excess AcOH at room temperature
(Table 4, entry 15). Interestingly, the formation of hydrothiolation product 5a increased to
4
1
5% yield upon increasing the amount of AcOH from 50 to 100 mol % (Table 4, entries 16-
9).
On this account, the further reaction was carried out with excess of AcOH (~10 vol) in
o
prolonged heating (15h) at 110 C, wherein the formation of 5a was dramatically increased to
7
2
5% yield and conditions involved were considered as optimized conditions (Table 4, entry
0). It was assumed that during the cyclocondensation of 2a and 3, the in situ eliminated
MeSH might be dissolved in excess of AcOH consequently the formation of 5a was
1
0

ACCEPTED MANUSCRIPT
predominant. Though the AcOH was taken as excess, we could not control the evaporation of
MeSH due its high volatile nature and it was acquired that it might have been escaped from
the reaction medium. Only the dissolved MeSH in AcOH reacts further with olefin 4 to give
5
. This could be the reason to obtain 5 as the major product though the formation of 4 (<10%)
was unavoidable as it is the intermediate for 5. Following the optimized reaction conditions
Table 4, entry 20) the one-pot tandem hydrothiolation was extended to various substrates 2a-
(
y (Table 5). This novel hydrothiolation reaction displayed high functional group tolerance
and proved to be a general protocol for the synthesis of thioethers.
Table 5. Synthesis of compounds 5a-y under optimized conditions via one-pot Tandem
a
hydrothiolation
O
H2N
H2N
H
N
Excess AcOH
110 oC,15 h,
Ar
MeS
N
MeS
a-y
SMe
66-75%
Ar
2
3
5a-y
H
N
H
H
H
N
N
N
MeS
N
MeS
MeO
N
MeS
N
MeS
MeS
N
OMe
Cl
5a (75%)
5b (72%)
5c (68%)
5e (69%)
H
N
H
N
H
N
H
N
MeS
N
N
MeS
F
N
MeS
N
F
Cl
F
5f (71%)
5g (74%)
5h (72%)
5i (70%)
H
N
H
N
H
N
H
N
MeS
N
MeS
N
MeS
F
N
MeS
Br
N
Br
CN
F
5j (66%)
5k (69%)
5l (66%)
5n (71%)
H
N
H
N
H
N
H
N
MeS
Cl
N
MeS
N
MeS
MeO
N
MeS
O2N
N
Br
Br
Cl
Cl
F
5o (68%)
5p (66%)
5q (73%)
5r (73%)
H
N
MeS
N
5s (69%)
a
Optimized Reaction conditions: 2 (1mol), 3 (1mol), excess AcOH, reflux, 110 ºC, 5h.
1
1

ACCEPTED MANUSCRIPT
Isolated yields refer to 2These tandem hydrothiolation included several variants of α-
aroylidineketene dithioacetal 2 bearing modifications in substitution of phenyl ring at ortho,
meta and para positions were explored to afford regioselective product 5 in good yields. The
hydrothiolation reaction with naphthyl variant of 2a resulted in the formation of 5s in 69%
1
13
yields. Compounds 5b-s were confirmed by H, C NMR and LC-MS analysis. Additional to
support of the analytical data, the structure of these compounds were confirmed on the basis
of single-crystal X-ray structural analysis of a representative product 5l of the series (Figure
2
9c
2
).
Figure 2. X-ray Crystal structure of 5l
The regioselective hydrothiolation was examined further using various α-
heteroaroylidineketene dithioacetals 2v-y incorporating heterocycles such as 2-furyl, 5-
bromo-3-pyridinyl, 2-thienyl and 5-bromo-2-thienyl in instead of phenyl ring of 2 under
optimized reaction conditions to furnish 5v-y in good yields (Table 6). This suggests that the
methodology has broad scope and can be extended to wide range of substrates.
Table 6. Synthesis of 5v-y during one-pot Tandem hydrothiolation reaction of 3 and α-
a
heteroaroylidineketene dithioacetals 2v-y
1
2

ACCEPTED MANUSCRIPT
O
H
H N
2
N
Excess AcOH
Het
o
1
10 C,15 h,
6
MeS
N
H N
2
MeS
SMe
Het
8-72%
2
v-y
3
5v-y
H
H
N
N
MeS
N
MeS
N
O
Br
N
5v (70%)
5w (72%)
H
N
H
N
MeS
N
S
MeS
N
S
Br
5y (71%)
5x (68%)
a
Optimized Reaction conditions: 2 (1mol), 3 (1mol), excess AcOH, reflux, 110 ºC, 15h.
In order to propose the probable mechanism and validate our initial hypothesis on the
formation of 4 and 5, the dehydrothiolation was attempted. The obvious possibility was that
either 4 or 5 formed first in the reaction which would further transform to other compound. In
this direction, dehydrothiolation of 5a in presence of several acids such as AcOH, HCOOH,
o
HCl (0.1 M), H SO (0.1 M) and p-TsOH.H O at 100 C was attempted (Scheme 3).
2
4
2
However, the dehydrothiolation was not successful to yield 4a under acidic condition at 100
o
C. It is therefore likely that the formation of olefin 4 precedes the formation of product 5 in
the reaction medium.
H
N
H
Acids
N
MeS
N
o
1
00 C, 15 h
N
5a
4a
Scheme 3. Attempted elimination of MeSH
The above hypothesis is further supported by the fact that 4g and 4n when reacted with 2-
aminoethane thiol and thiophenol in AcOH respectively to afford the corresponding
regioselective hydrothiolation products 8a and 8b (Table 7). As expected, the reaction of 4g
proceeded expeditiously to yield 8a with no trace of aza Michael adduct product.
1
3

ACCEPTED MANUSCRIPT
a
Table 7. Regioselective hydrothiolation of 4g&n in presence of AcOH
H
H
N
N
Ar
R-SH
N
SR
AcOH/100 °C,15h
N
Ar
4g&n
8a&b
N
F
N
N
H
F
N
H
S
F
S
NH2
8a (87%)
8b (85%)
a
Optimized Reaction conditions: 2 (1mol), 3 (1mol), excess AcOH, reflux, 110 ºC, 15h.
Isolated yields refer to 2.
On the basis of above experimental results, we propose a plausible mechanism for
formation of 4 and 5 as depicted in Scheme 4, which also highlights on appropriate selectivity
of the products in presence/absence of CuI. It is likely that initially oxygen of the carbonyl
group in 2 gets protonated followed by nucleophilic addition of amine group of 3 at C-1
position to give imine II. The imine II further cyclizes to afford 2-(2,2-bis(methylthio)vinyl)-
2
-phenyl-2,3-dihydro-1H-benzo[d]imidazole (III), which rapidly degrades to more stable 2-
styrylbenzimidazole 4 by concomitant elimination of ethynyl(methyl)sulfane 7 and MeSH 6.
At this stage, presence of CuI in the reaction medium is supposed to be determining outcome
of the reaction products. In presence of Cu catalyst, the hydrothiolation of 4 would be
inhibited since MeSH is likely to be trapped by the Cu atom thereby leading to selective
3
0
formation of compound 4. Based on a literature report, we anticipated that copper would
likely to form a complex with sulphur atom of thiol source thereby making the nucleophile
unavailable for further Michael-type addition. On the other hand, in the absence of CuI or any
copper salts, the in situ generated MeSH 6 would react with 4 via sulfa-Michael addition
under acidic conditions leading to hydrothiolated product 5.
1
4

ACCEPTED MANUSCRIPT
Scheme 4. Plausible mechanism proposed for the formation and selectivity of of 4 & 5
during reaction of 2 and 3
In conclusion, we have demonstrated selective routes for the synthesis of 2-styryl
benzimidazoles 4 and their hydrothiolated products 5 through optimization of the initial
reaction involving 2 and OPD 3. Selective synthesis of 4 was accomplished under acidic
conditions in presence of copper catalyst while that of 5 was a catalyst-free transformation.
Further, based on these results a plausible mechanism was proposed for the transformation of
2
and 3 under acidic conditions in the presence and absence of copper (I) salts. The current
work describes the potential of α-aroylidineketene dithioacetal as key synthetic intermediates.
It is worth to highlight here that our new strategy would provide a simple alternative method
for the hydrothiolation of broad range of substrates in the absence of metal catalysts.
Acknowledgements
The authors thank DST and UGC - MRP, New Delhi for the financial assistance. We thank
DST-IRHPA for funding’s towards high resolution NMR. Financial support from UGC-BSR
Meritorious to P.D is gratefully acknowledged for the award of a Senior Research
Fellowship. We also thank Dr. P. Thilagar, IPC, IISC, Bangalore for helping to analyse the
single crystal data.
Experimental Section
1
5

ACCEPTED MANUSCRIPT
General Consideration
The melting points reported in the work are uncorrected. Unless stated otherwise, solvents
and chemicals were obtained from commercial sources and used without further purification.
1
13
The H and CNMR spectra of the new compounds were measured at 400MHz or 300MHz
and 100MHz or 75MHz (mentioned in respective NMR data itself) respectively using Bruker
NMR instrument in DMSO-d or CDCl . Chemical shifts are reported in parts per million (δ),
6
3
coupling constants (J values) are reported in Hertz (Hz) relative to tetramethylsilane. Spin
multiplicities are indicated by the following symbols: s (singlet), d (doublet), t (triplet), m
(multiplet) dd (doublet of doublets), td (triplet of doublets) bs (broad singlet). Elemental
analysis was recorded on Thermofinnigan flash 2000 organic elemental CHNS analyser.
General procedure for the synthesis of 1,1-bis(methylthio)-5-arylpenta-1,4-dien-3-one
(2a-y)
To a solution of 4,4-bis(methylthio)but-3-en-2-one (1mol) in ethanol (10ml) was added
NaOH (1.5mol) and aryl aldehyde (1.1mol) under constant stirring. After the starting material
was consumed as indicated by TLC, the reaction mixture was poured into ice water and the
resulting solid was filtered, washed well with water (20 ml). The solid material obtained was
crystallized from ethanol to furnish 81-99% of 1,1-bis(methylthio)-5-arylpenta-1,4-dien-3-
one as a yellow solid.
2
8
(
E)-1,1-bis(methylthio)-5-phenylpenta-1,4-dien-3-one 2a: Pale yellow solid (2.5g, 81%);
1
M.pt.150 ⁰C; H NMR (400 MHz, DMSO-d ) δ : 7.68 (dd, J = 2 Hz, 8 Hz, 2H), 7.48 (d, J =
6
H
1
3
1
6 Hz, 1H), 7.38 - 7.44 (m, 3H), 7.07 (d, J = 16 Hz, 1H), 6.49 (s, 1H), 3.72 (s, 3H), 2.57 (s,
1
3
H), 2.44 (s, 3H); C NMR (75 MHz, DMSO-d ) δ : 183.5, 164.5, 140.4, 135.5, 130.4,
6
C
+
29.4, 128.6, 114.0, 17.2, 14.8; LC-MS calcd.m/z: 250, found 251 [(M+1)] .
(E)-5-(2-methoxyphenyl)-1,1-bis(methylthio)-penta-1,4-dien-3-one 2b: Yellow solid
(
2.9g, 85%); M.pt.116 ⁰C; [Found: C, 59.92; H, 5.71. C H O S requires C, 59.97; H, 5.75];
14
16
2 2
-1
1
IR
(ATR KBr cell, cm ) 1645, 1541; H NMR (400 MHz, DMSO-d ) δ : 7.72 (d, J = 16 Hz,
6 H
1
H), 7.66 (d, J = 6.4 Hz, 1H), 7.39 - 7.35 (m, 1H), 7.08 (s, 1H), 7.05 (d, J = 6.4 Hz, 1H), 6.98
1
3
(
t, J = 7.2 Hz, 1H), 6.42 (s, 1H), 3.85 (s, 3H), 2.55 (s, 3H), 2.44 (s, 3H); C NMR (100 MHz,
DMSO-d ) δ : 183.7, 164.2, 158.4, 135.2, 131.9, 128.5, 128.3, 123.8, 121.1, 114.6, 112.2,
6
C
+
5
6.1, 17.2, 14.8; LC-MS calcd.m/z 280, found 281 [(M+1)] .
1
6

ACCEPTED MANUSCRIPT
(E)-5-(3-methoxyphenyl)-1,1-bis(methylthio)-penta-1,4-dien-3-one 2c: Pale yellow solid
(
3.1g, 90%); M.pt.114 ⁰C; [Found: C, 59.94; H, 5.70. C H O S requires C, 59.97; H, 5.75];
1
4
16
2 2
-1
1
IR
(ATR KBr cell, cm ) 1771, 1684, 1577; H NMR (400 MHz, DMSO-d ) δ : 7.44 (d, J =
6 H
1
6 Hz, 1H), 7.32 (t, J = 8 Hz, 1H), 7.24 - 7.22 (m, 2H), 7.06 (d, J = 16.4 Hz, 1H), 6.96 - 6.94
13
(
m, 1H), 6.48 (s, 1H), 3.78 (s, 3H), 2.56 (s, 3H), 2.44 (s, 3H); C NMR (100 MHz, DMSO-
d ) δ : 183.6, 164.6, 160.1, 140.4, 136.9, 130.4, 128.9, 121.2, 116.4, 114.0, 113.2, 55.7, 17.3,
6
C
+
1
4.8; LC-MS calcd.m/z 280, found 281 [(M+1)] .
2
8
(
E)-5-(4-methoxyphenyl)-1,1-bis(methylthio)-penta-1,4-dien-3-one 2d: Yellow solid
1
(
3.1g, 90%); M.pt 104-106 ⁰C; H NMR (400 MHz, DMSO-d ) δ : 7.64 (d, J = 8.8 Hz, 2H),
6
H
7
.45 (d, J = 15.9 Hz, 1H), 6.98 (d, J = 8 Hz, 2H), 6.93 (d, J = 16 Hz, 1H), 6.45 (s, 1H), 3.79
1
3
(
s, 3H), 2.56 (s, 3H), 2.48 (s, 3H); C NMR (75 MHz, DMSO-d ) δ : 183.7, 163.5, 161.3,
6 C
1
40.4, 130.3, 128.0, 126.2, 114.9, 114.2, 55.8, 17.2, 14.8; LC-MS calcd.m/z 280, found 281
+
[
(M+1)] .
2
8
(
E)-5-(3-chlorophenyl)-1,1-bis(methylthio)penta-1,4-dien-3-one 2e: Pale yellow solid
1
(
2.9g, 85%); M.pt. 136 ⁰C; H NMR (400 MHz, DMSO-d ) δ : 7.79 (s, 1H), 7.65 - 7.62 (m,
6
H
1
3
1
H), 7.47 - 7.43 (m, 3H), 7.17 (d, J = 16 Hz, 1H), 6.49 (s, 1H), 2.57 (s, 3H), 2.46 (s, 3H); C
NMR (100 MHz, DMSO-d ) δ : 183.3, 165.2, 138.6, 137.8, 134.2, 131.2, 130.1, 129.9,
6
C
+
1
27.9, 127.3, 113.9, 17.3, 14.8; LC-MS calcd. m/z: 284, found 285 [(M+1)] .
2
8
(
E)-5-(4-chlorophenyl)-1,1-bis(methylthio)penta-1,4-dien-3-one 2f: Yellow solid (3.4g,
1
9
9%); M.pt.144 ⁰C; H NMR (400 MHz, DMSO-d ) δ : 7.69 (d, J = 8.4 Hz, 2H), 7.46 (d, J =
6
H
1
3
8
.4 Hz, 2H), 7.43 (s, 1H), 7.07 (d, J = 16 Hz, 1H), 6.47 (s, 1H), 2.48 (s, 3H), 2.46 (s, 3H); C
NMR (100 MHz, DMSO-d ) δ : 182.8, 164.4, 138.4, 134.3, 133.9, 129.7, 128.9, 128.8,
6
C
+
1
13.4, 16.7, 14.3; LC-MS calcd.m/z: 284, found 285 [(M+1)] .
2
8
(
E)-5-(2-fluorophenyl)-1,1-bis(methylthio)-penta-1,4-dien-3-one 2g: Pale yellow solid
1
(
3g, 92%); M.pt.109 ⁰C; H NMR (400 MHz, DMSO-d ) δ : 7.79 (t, J = 8 Hz, 1H), 7.53 (d, J
6
H
=
16.4 Hz, 1H), 7.46 - 7.42 (m, 1H), 7.29 - 7.23 (m, 2H), 7.15 (d, J = 15.6 Hz, 1H), 6.47 (s,
1
3
3
1
H), 2.57 (s, 3H), 2.45 (s, 3H); C NMR (75 MHz, DMSO-d ) δ : 183.7, 166.1, 163.1,
6 C
59.7, 133.8, 131.1, 130.9, 129.8, 129.4, 124.3, 123.3, 123.2, 116.2, 115.9, 113.1, 17.2, 15.1;
+
UPLC-MS calcd. m/z 268, found 269[(M+1)] .
1
7

ACCEPTED MANUSCRIPT
(E)-5-(3-fluorophenyl)-1,1-bis(methylthio)-penta-1,4-dien-3-one 2h: Pale yellow solid
(
2.9g, 90%); M.pt.124 ⁰C; [Found: C, 58.15; H, 4.83. C H FOS requires C, 58.18; H,
1
3
13
2
-1
1
4
.88]; IR
(ATR KBr cell, cm ) 1630, 1500, 1420; H NMR (400 MHz, DMSO-d ) δ : 7.56 -
6 H
7
.42 (m, 4H), 7.24 - 7.20 (m, 1H), 7.13 (d, J = 16.4 Hz, 2H), 6.47 (s, 1H), 2.57 (s, 3H), 2.45
1
3
(
s, 3H); C NMR (75 MHz, DMSO-d ) δ : 183.0, 166.2, 139.3, 130.1, 130.0, 123.9, 116.4,
6 C
+
1
16.2, 113.9, 113.7, 112.9, 17.0, 14.8; UPLC-MS calcd.m/z 268, found 269 [(M+1)] .
(E)-5-(4-fluorophenyl)-1,1-bis(methylthio)-penta-1,4-dien-3-one 2i: Pale yellow solid
(
3.0g, 92%); M.pt.116-118 ⁰C; [Found: C, 58.10; H, 4.81. C H FOS requires C, 58.18; H,
13
13
2
-1
1
4
.88]; IR (ATR KBr cell, cm ) 1640, 1598, 1465; H NMR (400 MHz, DMSO-d ) δ : 7.74
6 H
(t, J = 8.4 Hz, 2H), 7.47 (d, J = 16.4 Hz, 1H), 7.25 (t, J = 8.8 Hz, 2H), 7.01 (d, J = 16.4 Hz,
13
2
H), 6.46 (s, 1H), 2.55 (s, 3H), 2.43 (s, 3H); C NMR (75 MHz, DMSO-d ) δ : 183.5, 165.7,
6 C
1
62.3, 139.7, 129.9, 129.7, 127.0, 115.9, 115.6, 113.1, 17.2, 15.0; LC-MS calcd.m/z 268,
+
found 269 [(M+1)] .
(E)-5-(2-bromophenyl)-1,1-bis(methylthio)-penta-1,4-dien-3-one 2j: Pale yellow solid
(
3.57g, 88%); M.pt.108 ⁰C; [Found: C, 47.38; H, 3.92. C H BrOS requires C, 47.42; H,
1
3
13
2
-1
1
3
.98]; IR (ATR KBr cell, cm ) 2986, 1646, 1585; H NMR (400 MHz, DMSO-d ) δ : 7.88
6 H
(dd, J = 1.56 Hz, 7.84 Hz, 1H), 7.73 (d, J = 6.44 Hz, 1H), 7.70 (s, 1H), 7.46 (t, J = 6.96 Hz,
1
2
1
H), 7.35 (td, J = 1.64 Hz, 7.88 Hz, 1H), 7.16 (d, J = 15.7 Hz, 1H), 6.48 (s, 1H), 2.58 (s, 3H),
1
3
.48 (s, 3H); C NMR (100 MHz, DMSO-d ) δ : 182.8, 166.0, 137.9, 134.9, 133.7, 131.9,
6
C
+
31.3, 128.7, 128.4, 125.3, 114.3, 17.3, 14.9; LC-MS calcd.m/z 329, found 330 [(M+1)] .
(E)-5-(4-bromophenyl)-1,1-bis(methylthio)-penta-1,4-dien-3-one 2k: Pale yellow solid
(
3.45g, 85%); M.pt.148-150 ⁰C; [Found: C, 47.35; H, 3.94. C H BrOS requires C, 47.42;
1
3
13
2
-1
1
H, 3.98]; IR (ATR KBr cell, cm ) 2914, 1741, 1645, 1580; H NMR (400 MHz, DMSO-d )
6
δH: 7.63 - 7.59 (m, 4H), 7.44 (d, J = 16 Hz, 1H), 7.08 (d, J = 15.6 Hz, 2H), 6.47 (s, 1H), 2.56
1
3
(
s, 3H), 2.44 (s, 3H); C NMR (75 MHz, DMSO-d ) δ : 183.2, 166.1, 139.5, 134.1, 131.8,
6 C
+
1
29.3, 127.7, 123.8, 113.0, 17.2, 15.0; LC-MS calcd.m/z 329, found 330 [(M+1)] .
(E)-4-(5,5-bis(methylthio)-3-oxopenta-1,4-dienyl)benzonitrile 2l: Pale yellow solid (3.02g,
8
4
9%); M.pt.218 ⁰C; [Found: C, 61.01; H, 4.73, N, 5.02. C H NOS requires C, 61.06; H,
1
4
13
2
-1
1
.76; N, 5.09]; IR (ATR KBr cell, cm ) 2200, 1630, 1580; H NMR (400 MHz, DMSO-d )
6
δH: 7.86 - 7.84 (m, 4H), 7.51 (d, J = 16 Hz, 1H), 7.22 (d, J = 16.4 Hz, 1H), 6.50 (s, 1H), 2.57
1
8

ACCEPTED MANUSCRIPT
1
3
(
s, 3H), 2.45 (s, 3H); C NMR (75 MHz, DMSO-d ) δ : 182.2, 167.0, 139.2, 137.9, 132.0,
6 C
+
1
30.1, 127.9, 112.5, 112.1, 16.8, 14.6; LC-MS calcd.m/z 275, found 276 [(M+1)] .
(E)-1,1-bis(methylthio)-5-(4-nitrophenyl)-penta-1,4-dien-3-one 2m: Pale yellow solid
(
3.38g, 93%); M.pt. 224-226 ⁰C; [Found: C, 52,82; H, 4.38, N, 4.70. C H NO S requires
1
3
13
3 2
-1
1
C, 52.86; H, 4.44; N, 4.74]; IR (ATR KBr cell, cm ) 1644, 1584, 1508, 1467; H NMR (400
MHz, DMSO-d ) δ : 8.26 (d, J = 8.8 Hz, 2H), 7.95 (d, J = 8.8 Hz, 2H), 7.58 (d, J = 16 Hz,
6
H
1
3
1
H), 7.29 (d, J = 16 Hz, 1H), 6.54 (s, 1H), 2.59 (s, 3H), 2.49 (s, 3H); C NMR (100 MHz,
DMSO-d ) δ : 182.6, 166.3, 135.3, 135.0, 133.9, 132.3, 131.8, 129.9, 129.4, 128.4, 114.2,
6
C
+
1
7.3, 14.8; LC-MS calcd.m/z 295, found 296 [(M+1)] .
2
8
(E)-5-(2,4-difluorophenyl)-1,1-bis(methylthio)penta-1,4-dien-3-one 2n:
Pale yellow
1
solid (3.1g, 88%); M.pt.152-154 ⁰C; H NMR (400 MHz, DMSO-d ) δ : 7.89 (q, J = 15.6
6
H
Hz, 1H), 7.47 (d, J = 15.6 Hz, 1H), 7.31 - 7.35 (m, 1H), 7.18 - 7.15 (m, 1H), 7.11 (d, J = 16
1
3
Hz, 1H), 6.45 (s, 1H), 2.56 (s, 3H), 2.44 (s, 3H); C NMR (100 MHz, DMSO-d ) δ : 182.5,
6
C
1
1
65.1, 164.3, 164.1, 162.1, 161.6, 159.5, 130.4, 130.3, 130.5, 119.5, 119.4, 113.6, 112.5,
+
12.3, 112.2, 104.8, 104.3, 16.7, 14.3; LC-MS calcd. m/z 286, found 287 [(M+1)] .
2
8
(E)-5-(2,4-dichlorophenyl)-1,1-bis(methylthio)penta-1,4-dien-3-one 2o:
Pale yellow
1
solid (3.9g, 99%); M.pt.126 ⁰C; H NMR (400 MHz, DMSO-d ) δ : 7.69 (d, J = 8.4 Hz, 1H),
6
H
7
5
1
.59 (d, J = 8.4 Hz, 1H), 7.50 (s, 1H), 7.43 (d, J = 8.4 Hz, 1H), 6.17 (s, 1H), 5.55 (s, 1H),
13
.31 - 5.27 (m, 1H), 2.45 (s, 3H), 2.40 (s, 3H); C NMR (100 MHz, DMSO-d ) δ : 182.6,
6
C
66.3, 135.3, 135.0, 133.9, 132.3, 131.8, 129.9, 129.4, 128.4, 114.3, 17.3, 14.8; LC-MS
+
calcd.m/z 319, found 320 [(M+1)] .
2
8
(E)-5-(5-bromo-2-methoxyphenyl)-1,1-bis(methylthio)penta-1,4-dien-3-one 2p:
Pale
1
yellow solid (3.85g, 87%); M.pt.156-158 ⁰C; H NMR (400 MHz, DMSO-d ) δ : 7.88 (s,
6
H
1
H), 7.61 (d, J = 15.6 Hz, 1H), 7.51 (d, J = 8.8 Hz, 1H), 7.15 (d, J = 16.4 Hz, 1H), 7.04 (d, J
1
3
=
8.8 Hz, 1H), 6.44 (s, 1H), 3.86 (s, 3H), 2.56 (s, 3H), 2.45 (s, 3H); C NMR (75 MHz,
DMSO-d ) δ : 183.3, 165.0, 157.4, 134.0, 133.2, 130.1, 129.9, 126.1, 114.6, 112.8, 56.5,
6
C
+
1
7.2, 14.8; LC-MS calcd.m/z 359, found 360 [(M+1)] .
(E)-5-(3-bromo-4-fluorophenyl)-1,1-bis(methylthio)-penta-1,4-dien-3-one
2q:
Pale
yellow solid (3.73g, 87%); M.pt.135-137 ⁰C; [Found: C, 44.92; H, 3.42. C H BrFOS : C,
13
12
2
-1
1
4
4.96; H, 3.48]; IR (ATR KBr cell, cm ) 1604, 1440; H NMR (400 MHz, DMSO-d ) δ :
6 H
1
9

ACCEPTED MANUSCRIPT
8
6
1
.08 (d, J = 16 Hz, 2H), 7.74 - 7.71 (m, 1H), 7.45 - 7.38 (m, 2H), 7.10 (d, J = 16 Hz, 1H),
13
.45 (s, 1H), 2.55 (s, 3H), 2.44 (s, 3H); C NMR (75 MHz, DMSO-d ) δ : 182.7, 166.4,
6
C
37.8, 132.7, 132.3, 128.6, 127.9, 116.6, 116.3, 112.8, 109.4, 109.1, 17.0, 14.8; LC-MS
+
calcd. m/z 347, found 348 [(M+1)] .
(E)-5-(2-chloro-5-nitrophenyl)-1,1-bis(methylthio)penta-1,4-dien-3-one 2r: Pale yellow
solid (3.79g, 93%); M.pt.158 ⁰C; [Found: C, 47.30; H, 3.65, N, 4.20. C H ClNO S requires
13
12
3 2
-1
1
C, 47.34; H, 3.67; N, 4.25]; IR
(ATR KBr cell, cm ) 1650, 1560, 1480; H NMR (400 MHz,
DMSO-d ) δ : 8.65 (s, 1H), 8.20 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.70 (d, J = 8.4
6
H
1
3
Hz, 1H), 7.44 (d, J = 8 Hz, 1H), 6.54 (s, 1H), 2.58 (s, 3H), 2.47 (s, 3H); C NMR (100 MHz,
DMSO-d ) δ : 182.2, 167.1, 147.3, 140.4, 134.7, 133.6, 133.0, 132.0, 125.6, 122.6, 114.5,
6
C
+
1
7.4, 14.9; LC-MS calcd. m/z 329, found 330 [(M+1)] .
(E)-1,1-bis(methylthio)-5-(naphthalene-1-yl)penta-1,4-dien-3-one 2s: Pale yellow solid
(
3.37g, 91%); M.pt.104 ⁰C; [Found: C, 67.92; H, 5.30.C H OS : C, 67.96; H, 5.37]; IR
1
7
16
2
-1
1
(
ATR KBr cell, cm ) 2981, 1645, 1509, 1484; H NMR (400 MHz, DMSO-d ) δ : 8.28 (t, J
6 H
=
15.2 Hz, 2H), 7.99 (t, J = 8 Hz, 1H), 7.93 (d, J = 4.2 Hz, 1H), 7.64 - 7.54 (m, 3H), 7.14 (d,
13
J = 16 Hz, 1H), 6.57 (s, 1H), 2.59 (s, 3H), 2.48 (s, 3H); C NMR (100 MHz, DMSO-d ) δ :
6
C
1
1
83.4, 165.1, 136.6, 133.8, 132.3, 131.5, 131.2, 130.6, 129.2, 127.5, 126.7, 126.2, 125.3,
+
23.7, 114.1, 17.3, 14.8; LC-MS calcd.m/z: 300, found 301 [(M+1)] .
(
E)-5-(anthracen-9-yl)-1,1-bis(methylthio)penta-1,4-dien-3-one 2t: Yellow solid (3.97g,
2%); M.pt.102-104 ⁰C; [Found: C, 71.92; H, 5.10.C H OS : C, 71.96; H, 5.18]; IR ATR
KBr cell, cm ) 1650, 1570; H NMR (400 MHz, DMSO-d ) δ : 8.68 (s, 1H), 8.39 (d, J =
9
(
21
18
2
-1
1
6
H
1
6.4 Hz, 1H), 8.21 (d, J = 8 Hz, 2H), 8.12 (d, J = 8.4 Hz, 2H), 7.58 - 7.54 (m, 4H), 6.88 (d, J
1
3
=
16.4 Hz, 1H), 6.61 (s, 1H), 2.56 (s, 3H), 2.48 (s, 3H); C NMR (75 MHz, DMSO-d ) δ :
6 C
1
1
83.9, 167.6, 139.1, 136.8, 132.0, 131.4, 130.2, 129.5, 128.5, 126.8, 126.3, 126.0, 114.0,
+
8.0, 15.9; LC-MS calcd.m/z: 350, found 351 [(M+1)] .
(
E)-1,1-bis(methylthio)-5-(pyren-1-yl)penta-1,4-dien-3-one 2u: Brown solid (3.87g, 84%);
M.pt.162-168 ⁰C; [Found: C, 73.71; H, 4.80.C H OS : C, 73.76; H, 4.84]; IR ATR KBr
cell, cm ) 1638, 1577; H NMR (400 MHz, DMSO-d ) δ : 8.60 (d, J = 13.6 Hz, 2H), 8.51 -
(
23
18
2
-1
1
6
H
8
1
1
.41 (m, 2H), 8.39 - 8.14 (m, 8H), 8.10 (t, J = 8 Hz, 1H), 7.38 (d, J = 15.2 Hz, 1H), 6.64 (s,
1
3
H), 2.62 (s, 6H); C NMR (75 MHz, DMSO-d ) δ : 194.0, 183.4, 165.1, 132.4, 131.3,
6
C
31.0, 130.9, 130.7, 129.6, 129.3, 128.9, 128.7, 127.7, 127.6, 127.2, 126.9, 126.4, 126.1,
2
0

ACCEPTED MANUSCRIPT
1
25.6, 125.2, 124.7, 124.6, 124.3, 123.0, 122.8, 114.3, 17.1, 14.7; LC-MS calcd.m/z: 374,
+
found 375 [(M+1)] .
2
8
(
E)-5-(furan-2-yl)-1,1-bis(methylthio)penta-1,4-dien-3-one 2v: Low melting solid (2.6g,
1
8
1
3
1
7%); H NMR (400 MHz, DMSO-d ) δ : 7.81 (s, 1H), 7.29 (d, J = 15.6 Hz, 1H), 6.86 (s,
6 H
H), 6.75 (d, J = 15.6 Hz, 1H), 6.61 - 6.60 (m, 2H), 6.43 (s, 1H), 2.54 (s, 3H), 2.42 (s,
1
3
H), C NMR (75 MHz, DMSO-d ) δ : 183.1, 164.4, 151.7, 145.8, 127.4, 125.7, 115.7,
6
C
+
14.1, 113.3, 17.2, 14.8; LC-MS calcd.m/z 240, found 241 [(M+1)] .
28
(
E)-5-(5-bromopyridin-3-yl)-1,1-bis(methylthio)penta-1,4-dien-3-one 2w: Pale yellow
1
solid (3.3g, 82%); M.pt.146 ⁰C; H NMR (400 MHz, DMSO-d ) δ : 8.82 (s, 1H), 8.67 (s,
6
H
1
3
1
H), 8.41 (s, 1H), 7.45 (d, J = 16.0 Hz, 1H), 7.29 (d, J = 16.0 Hz, 1H), 6.46 (s, 1H), 2.57 (s,
1
3
H), 2.45 (s, 3H); C NMR (100 MHz, DMSO-d ) δ : 182.8, 166.0, 151.2, 148.5, 137.0,
6
C
+
35.2, 133.4, 132.0, 121.1, 113.8, 17.3, 14.8; LC-MS calcd.m/z 329 found 330 [(M+1)] .
2
8
(
E)-1,1-bis(methylthio)-5-(thiphen-2-yl)-penta-1,4-dien-3-one 2x: Brown solid (2.71g,
1
8
7
2
1
6%); M.pt. 90 ⁰C; H NMR (400 MHz, DMSO-d ) δ : 7.89 (s, 1H), 7.59 - 7.61 (m, 1H),
6
H
.49 (d, J = 16.0 Hz, 1H), 7.48 (s, 1H), 6.86 (d, J = 15.6 Hz, 1H), 6.42 (s, 1H), 2.55 (s, 3H),
1
3
.43 (s, 3H); C NMR (75 MHz, DMSO-d ) δ : 164.4, 145.8, 142.5, 127.4, 125.7, 115.7,
6
C
14.1, 113.7, 113.3, 110.7, 107.3, 56.0, 17.2, 14.8; LC-MS calcd.m/z 256, found 257
+
[
(M+1)] .
(E)-5-(5-bromothiophen-2-yl)-1,1-bis(methylthio)-penta-1,4-dien-3-one 2y: Brown solid
(
3.55g, 86%); M.pt. 99 ⁰C; [Found: C, 39.35; H, 3.28. C H BrOS requires C, 39.40; H,
11
11
3
-
1
1
3
7
1
1
.31]; IR
(ATR KBr cell, cm ) 1798, 1633, 1574, 1453; H NMR (400 MHz, DMSO-d ) δ :
6 H
.55 (d, J = 15.6 Hz, 1H), 7.28 (dd, J = 4 Hz, 21.2 Hz, 2H), 6.71 (d, J = 15.6 Hz, 1H), 6.43 (s,
13
H), 2.55 (s, 3H), 2.43 (s, 3H); C NMR (75 MHz, DMSO-d ) δ : 183.7, 166.1, 133.8,
6
C
31.1, 130.9, 129.8, 129.3, 123.2, 115.9, 113.1, 17.2, 15.0; LC-MS calcd.m/z 335, found 336
+
[
(M+1)] .
General procedure for the preparation of (E)-aryl-1H-benzo[d]-benzimidazole (4a-y)
To a solution of (E)-1,1-bis(methylthio)-5-arylpenta-1,4-dien-3-one (1mol) in water (5mL)
was added 1,2-phenylenediamine (1mol) followed by glacial acetic acid (0.05mol). Finally,
CuI (10 mol%) was added to the mixture. The reaction was stirred magnetically reflux at 100
ºC for the indicated time (Table 5). After completion of the reaction (monitored by TLC), the
2
1

ACCEPTED MANUSCRIPT
product was extracted with ethyl acetate (15mL) and purified by column chromatography
(silica gel) using ethyl acetate/petroleum ether mixture as a gradient elution to afford product
(4a-y).
3
1
(
E)-2-styryl-1H-benzo[d]imidazole 4a: Off white solid (0.24g, 92%); M.pt.205-206 ⁰C; R
f
1
=
0.29 (hexane/ethylacetate 7:3); H NMR (400 MHz, DMSO-d ) δ : 12.58 (s, 1H), 7.54 -
6
H
13
7
.66 (m, 4H), 7.57 - 7.43 (m, 3H), 7.36 (d, J = 7.6 Hz, 1H), 7.27 (d, J = 8 Hz, 3H); C NMR
(
75 MHz, DMSO-d ) δ : 151.2, 138.9, 135.6, 134.8, 128.5,* 126.6, 122.2, 116.9, 114.6; LC-
6
C
+
MS calcd.m/z 220, found 221 [(M+1)] . *[Two carbon signals merged together]
32
(
E)-2-(2-methoxystyryl)-1H-benzo[d]imidazole 4b: Off white solid (0.22g, 83%);
M.pt.186-188 ⁰C; R = 0.25 (hexane/ethylacetate 7:3); [Found: C, 76.71; H, 5.60; N, 11.15.
f
-1
C H N O requires C, 76.78; H, 5.64; N, 11.19]; IR (ATR KBr cell, cm ) 3042, 2384, 1645,
16
14
2
1
1
7
3
1
570, 1402; H NMR (400 MHz, DMSO-d ) δ : 12.58 (s, 1H), 7.87 (d, J = 16.8 Hz, 1H),
6 H
.67 (d, J = 7.2 Hz, 1H), 7.48 (s, 2H), 7.35 (t, J = 8.4 Hz, 1H), 7.32 - 6.98 (m, 5H), 3.90 (s,
1
3
H); C NMR (75 MHz, DMSO-d ) δ : 157.6, 151.8, 130.6, 129.6, 127.6, 124.7, 121.3,
6
C
+
18.5, 112.1, 56.1; LC-MS calcd.m/z 250, found 251 [(M+1)] .
3
2
(
E)-2-(3-methoxystyryl)-1H-benzo[d]imidazole 4c: Off white solid (0.21g, 80%);
M.pt.175-177 ⁰C; R = 0.23 (hexane/ethylacetate 7:3); [Found: C, 76.75; H, 5.58; N, 11.11.
f
-1
C H N O requires C, 76.78; H, 5.64; N, 11.19]; IR (ATR KBr cell, cm ) 3053, 2366, 1645,
16
14
2
1
1
7
3
1
589, 1417; H NMR (400 MHz, DMSO-d ) δ : 12.57 (s, 1H), 7.61 (d, J = 16.8 Hz, 2H),
6 H
.46 (d, J = 8 Hz, 1H), 7.35 (t, J = 8 Hz, 1H), 7.24 - 7.14 (m, 5H), 6.93 (d, J = 8.4 Hz, 1H),
1
3
.81 (s, 3H); C NMR (75 MHz, DMSO-d ) δ : 156.7, 151.4, 132.7, 129.6, 128.0, 127.1,
6
C
+
22.6, 120.0, 114.4, 113.0, 56.5; LC-MS calcd.m/z 250, found 251 [(M+1)] .
3
2
(
E)-2-(4-methoxystyryl)-1H-benzo[d]imidazole 4d: Off white solid (0.23g, 87%);
M.pt.184-186 ⁰C; R = 0.21 (hexane/ethylacetate 7:3); [Found: C, 76.72; H, 5.60; N, 11.15.
f
-1
C H N O requires C, 76.78; H, 5.64; N, 11.19]; IR (ATR KBr cell, cm ) 3049, 2348, 1635,
16
14
2
1
1
574, 1480, 1258, 743; H NMR (400 MHz, DMSO-d ) δ : 12.57 (s, 1H), 7.88 (d, J = 16.8
6 H
Hz, 1H), 7.67 (d, J = 7.2 Hz, 1H), 7.49 (bs, 2H), 7.35 (t, J = 6.8 Hz, 1H), 7.20 (d, J = 16.8
Hz, 1H), 7.51 - 7.14 (m, 2H), 7.09 (t, J = 8.4 Hz, 1H), 7.01 (t, J = 7.6 Hz, 1H), 3.90 (s, 3H);
1
3
C NMR (75 MHz, DMSO-d ) δ : 157.1, 151.4, 130.1, 129.2, 127.1, 124.2, 121.9, 120.8,
6
C
+
1
18.0, 111.6, 55.6; LC-MS calcd.m/z 250, found 251 [(M+1)] .
2
2

ACCEPTED MANUSCRIPT
3
2,33
(E)-2-(3-chlorostyryl)-1H-benzo[d]imidazole 4e:
Off white solid (0.228g, 85%);
M.pt.229-230 ⁰C; R = 0.32 (hexane/ethylacetate 7:3); [Found: C, 70.67; H, 4.30; N, 10.97.
f
-1
C H ClN requires C, 70.73; H, 4.35; N, 11.00]; IR (ATR KBr cell, cm ). 3049, 1665,
15
11
2
1
1
3
427, 742; H NMR (400 MHz, DMSO-d ) δ :, 12.60 (s, 1H), 7.74 (s, 1H), 7.64 - 7.58 (m,
6 H
1
3
H), 7.49 - 7.38 (m, 3H), 7.29 (d, J = 16.4 Hz, 1H), 7.21 - 7.10 (m, 2H); C NMR (75 MHz,
DMSO-d ) δ : 150.4, 138.1, 133.8, 132.6, 130.7, 128.4, 126.4, 125.7, 122.7, 119.4; LC-MS
6
C
+
calcd. m/z 254, found 255 [(M+1)] .
32,33
(E)-2-(4-chlorostyryl)-1H-benzo[d]imidazole 4f:
Off white solid (0.225g, 84%);
M.pt.239-241 ⁰C; R = 0.40 (hexane/ethylacetate 7:3); [Found: C, 70.70; H, 4.35; N, 10.95.
f
-1
C H ClN requires C, 70.73; H, 4.35; N, 11.00]; IR (ATR KBr cell, cm ) 3049, 1650, 1430,
15
11
2
1
7
46; H NMR (400 MHz, DMSO-d ) δ : 12.60 (s, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.65 - 7.57
6
H
1
3
(
m, 2H), 7.48 (d, J = 8.4 Hz, 3H), 7.22 (d, J = 16.4 Hz, 3H), 7.19 - 7.13 (m, 4H); C NMR
75 MHz, DMSO-d ) δ : 151.4, 136.2, 134.7, 129.4, 129.3, 127.5, 122.1, 118.2; LC-MS
(
6
C
+
calcd.m/z 254, found 255 [(M+1)] .
3
2
(E)-2-(2-fluorostyryl)-1H-benzo[d]imidazole 4g:
Off white solid (0.237g, 89%);
M.pt.180-182 ⁰C; R = 0.32 (hexane/ethylacetate 7:3); [Found: C, 75.58; H, 4.58; N, 11.71.
f
-1
C H FN requires C, 75.62; H, 4.65; N, 11.76]; IR (ATR KBr cell, cm ) 3012, 2178, 1482,
15
11
2
1
1
1
7
1
419, 1225, 1023, 963; H NMR (400 MHz, DMSO-d ) δ : 12.76 (s, 1H), 7.85 (t, J = 7.6 Hz,
6 H
H), 7.76 (d, J = 16.4 Hz, 1H), 7.54 (s, 2H), 7.42 (q, J = 7.2 Hz, 1H), 7.32 - 7.26 (m, 3H),
1
3
.19 - 7.16 (m, 2H); C NMR (75 MHz, DMSO-d ) δ : 161.7, 158.4, 150.7, 138.7, 129.5,
6
C
29.4, 127.2, 127.1, 126.7, 123.9, 123.4, 123.2, 121.9, 119.3, 115.1, 114.4; LC-MS calcd.
+
m/z 238, found 239 [(M+1)] .
3
2
(E)-2-(3-fluorostyryl)-1H-benzo[d]imidazole 4h:
Off white solid (0.229g, 86%);
M.pt.216-218 ⁰C; R = 0.36 (hexane/ethylacetate 7:3); [Found: C, 75.55; H, 4.61; N, 11.70.
f
-1
C H FN requires C, 75.62; H, 4.65; N, 11.76]; IR (ATR KBr cell, cm ) 3049, 1456, 1320,
15
11
2
1
1
012; H NMR (400 MHz, DMSO-d ) δ : 12.65 (s, 1H), 7.64 (d, J = 16.4 Hz, 1H), 7.54 -
6 H
1
3
7
.52 (m, 3H), 7.48 - 7.45 (m, 2H), 7.28 (d, J =16.4 Hz, 1H), 7.18 - 7.15 (m, 3H); C NMR
(
75 MHz, DMSO-d ) δ : 163.8, 163.3, 160.5, 150.0, 138.5, 138.0, 137.7, 132.6, 129.7, 122.0,
6 C
+
1
21.7, 118.0, 114.2, 112.4, 112.1; LC-MS calcd.m/z 238, found 239 [(M+1)] .
(E)-2-(4-fluorostyryl)-1H-benzo[d]imidazole 4i: Off white solid (0.23g, 87%); M.pt. 116-
1
18 ⁰C; R = 0.28 (hexane/ethylacetate 7:3); [Found: C, 75.58; H, 4.60; N, 11.72. C H FN
f
15 11
2
2
3

ACCEPTED MANUSCRIPT
-1
1
requires C, 75.62; H, 4.65; N, 11.76]; IR
(
ATR KBr cell, cm ) 3023, 1575, 1480; H NMR
(
-
400 MHz, DMSO-d ) δ : 12.66 (s, 1H), 7.74 - 7.70 (m, 2H), 7.65 (d, J = 16.4 Hz, 1H), 7.55
6
H
1
3
7.51 (m, 2H), 7.27 (d, J = 8.8 Hz, 2H), 7.19 - 7.15 (m, 3H); C NMR (100 MHz, DMSO-
d ) δ : 164.0, 161.6, 151.3, 133.5, 132.9, 132.8, 129.6, 129.5, 122.5, 118.1, 116.5, 116.2; LC-
6
C
+
MS calcd.m/z 238, found 239 [(M+1)] .
3
2
(
E)-2-(2-bromostyryl)-1H-benzo[d]imidazole 4j: Off white solid (0.23g, 85%); M.pt.190-
1
92 ⁰C; R = 0.30 (hexane/ethylacetate 7:3); [Found: C, 60.19; H, 3.66; N, 9.29. C H BrN
f
15 11
2
-1
1
requires C, 60.22; H, 3.71; N, 9.36]; IR (ATR KBr cell, cm ) 3045, 2456, 1785, 1520; H
NMR (400 MHz, DMSO-d ) δ : 12.74 (s, 1H), 7.92 - 7.87 (m, 2H), 7.70 (d, J = 7.6 Hz, 1H),
6
H
7
.62 (d, J = 7.6 Hz, 2H), 7.49 (q, J = 8 Hz, 2H), 7.30 (t, J = 7.6 Hz, 1H), 7.23 - 7.15 (m, 3H);
C NMR (75 MHz, DMSO-d ) δ : 150.3, 135.3, 133.0, 131.8, 130.2, 129.4, 128.2, 127.3,
1
3
6
C
+
1
23.5, 122.1, 120.7; LC-MS calcd.m/z 299, found 300 [(M+1)] .
3
2
(E)-2-(4-bromostyryl)-1H-benzo[d]imidazole 4k:
Off white solid (0.226g, 83%);
M.pt.250-252 ⁰C; R = 0.25 (hexane/ethylacetate 7:3); [Found: C, 60.15; H, 3.67; N, 9.30.
f
-1
C H BrN requires C, 60.22; H, 3.71; N, 9.36]; IR (ATR KBr cell, cm ) 3057, 2364, 1645,
15
11
2
1
1
485, 1427, 968, 738; H NMR (400 MHz, DMSO-d ) δ : 12.60 (s, 1H), 7.63 - 7.57 (m, 6H),
6 H
1
3
7
.47 (d, J = 7.6 Hz, 1H), 7.23 (d, J = 16.8 Hz, 1H), 7.19 - 7.13 (m, 2H); C NMR (75 MHz,
DMSO-d ) δ : 149.5, 133.8, 131.8, 130.5, 127.3, 120.8, 117.1; LC-MS calcd.m/z 299, found
6
C
+
3
00 [(M+1)] .
9b,c
(
E)-4-(2-(1H-benzo[d]imidazol-2-yl)vinyl)benzonitile 4l: Off white solid (0.235g, 88%);
M.pt.240-241 ⁰C; R = 0.13 (hexane/ethylacetate 7:3); [Found: C, 78.29; H, 4.49; N, 17.08.
f
-1
C H N requires C, 78.35; H, 4.52; N, 17.13]; IR (ATR KBr cell, cm ) 3525, 3055, 2364,
16
11
3
1
2
7
224, 1599, 1417, 817, 732; H NMR (400 MHz, DMSO-d ) δ : 12.70 (s, 1H), 7.86 (s, 4H),
6 H
13
.69 (d, J = 18 Hz, 1H), 7.58 - 7.52 (m, 2H), 7.39 (d, J = 16.4 Hz, 1H), 7.19 (s, 2H); C
NMR (75 MHz, DMSO-d ) δ : 151.6, 139.1, 129.1, 128.0, 127.6, 126.8, 126.1, 125.7, 122.5,
6
C
+
1
17.9, 73.9; LC-MS calcd.m/z 245, found 246 [(M+1)] .
2
0b
(E)-2-(4-nitrostyryl)-1H-benzo[d]imidazole 4m:
Pale yellow solid (0.239g, 89%);
M.pt.257-258 ⁰C; R = 0.18 (hexane/ethylacetate 7:3); [Found: C, 67.90; H, 4.14; N, 15.80.
f
-1
C H N O requires C, 67.92; H, 4.18; N, 15.84]; IR (ATR KBr cell, cm ) 2366, 1591,
15
11
3
2
1
1
506, 1336, 759; H NMR (400 MHz, DMSO-d ): δ : 12.70 (s, 1H), 8.26 (d, J = 8.8 Hz, 2H),
6 H
7
.93 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 16.4 Hz, 1H), 7.62 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 7.6
2
4

ACCEPTED MANUSCRIPT
1
3
Hz, 1H), 7.45 (d, J = 16.8 Hz, 1H), 7.24 - 7.16 (m, 2H); C NMR (100 MHz, DMSO-d ) δ :
6
C
1
2
50.5, 147.3, 142.9, 132.2, 129.4, 128.4, 124.6, 124.4, 122.6; LC-MS calcd.m/z 265, found
+
66 [(M+1)] .
(E)-2-(2,4-difluorostyryl)-1H-benzo[d]imidazole 4n: Off white solid (0.244g, 91%);
M.pt.218-221 ⁰C; R = 0.30 (hexane/ethylacetate 7:3); [Found: C, 70.28; H, 3.90; N, 10.87.
f
-1
C H F N requires C, 70.31; H, 3.93; N, 10.93]; IR (ATR KBr cell, cm ) 3310, 1581, 1480;
15
10
2
2
1
H NMR (400 MHz, DMSO-d ) δ : 12.67 (s, 1H), 7.94 (q, J = 8.4 Hz, 1H), 7.70 (d, J = 16.8
6
H
Hz, 1H), 7.58 - 7.48 (m, 2H), 7.35 (t, J = 9.6 Hz, 1H), 7.26 (d, J = 16.4 Hz, 1H), 7.17 (s, 2H);
1
3
C NMR (75 MHz, DMSO-d ) δ : 164.3, 162.3, 162.2, 161.0, 159.0, 158.8, 151.0, 129.9,
6
C
1
29.8, 129.7, 125.6, 122.7, 120.7, 120.5, 112.9, 112.7, 105.3, 104.6; LC-MS calcd.m/z 256,
+
found 257 [(M+1)] .
3
2
(
E)-2-(2,4-dichlorostyryl)-1H-benzo[d]imidazole 4o: Off white solid (0.245g, 90%);
M.pt.240-241 ⁰C; R = 0.37 (hexane/ethylacetate 7:3); [Found: C, 62.28; H, 3.44; N, 9.65.
f
-1
C H Cl N requires C, 62.30; H, 3.49; N, 9.69]; IR (ATR KBr cell, cm ) 3055, 1641, 1581,
15
10
2
2
1
1
7
7
1
2
427, 958, 742; H NMR (400 MHz, DMSO-d ) δ : 12.77 (s, 1H), 7.98 (d, J = 8.4 Hz, 2H),
6 H
.87 (d, J = 16.4 Hz, 1H), 7.69 (s, 1H), 7.61 (d, J = 7.6 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H),
1
3
.29 (d, J = 16 Hz, 1H), 7.23 - 7.15 (m, 2H); C NMR (75 MHz, DMSO-d ) δ : 150.7,
6
C
34.1, 133.9, 133.2, 129.8, 128.9, 128.5, 128.4, 122.3, 121.9; LC-MS calcd.m/z 289, found
+
90 [(M+1)] .
(E)-2-(5-bromo-2-methoxystyryl)-1H-benzo[d]imidazole 4p: Off white solid (0.23g, 84%);
M.pt.235-237 ⁰C; R = 0.26 (hexane/ethylacetate 7:3); [Found: C, 58.32; H, 3.94; N, 8.49.
f
-1
C H BrN O requires C, 58.38; H, 3.98; N, 8.51]; IR (ATR KBr cell, cm ) 2958, 2360,
16
13
2
1
1
7
741, 1483, 1259, 1024, 802, 742; H NMR (400 MHz, DMSO-d ) δ : 12.60 (s, 1H), 7.85 -
6 H
.84 (m, 1H), 7.80 (d, J = 16.0 Hz, 1H), 7.58 (d, J = 7.6 Hz, 1H), 7.50 - 7.45 (m, 2H), 7.27
1
3
(
d, J = 16.6 Hz, 1H), 7.17 - 7.14 (m, 2H), 7.06 (d, J = 8.8 Hz, 2H); C NMR (100 MHz,
DMSO-d ) δ : 159.7, 137.2, 134.2, 130.0, 122.1, 119.6, 118.1, 114.7, 111.8, 56.1; LC-MS
6
C
+
calcd.m/z 329, found 330 [(M+1)] .
(E)-2-(3-bromo-4-fluorostyryl)-1H-benzo[d]imidazole 4q: Off white solid (0.225g, 82%);
M.pt.170-171 ⁰C; R = 0.29 (hexane/ethylacetate 7:3); [Found: C, 56.77; H, 3.12; N, 8.80.
f
-1
C H BrFN requires C, 56.81; H, 3.18; N, 8.83]; IR (ATR KBr cell, cm ) 3566, 2926, 2362,
15
10
2
1
1
743, 1491, 1437, 1257, 810, 732; H NMR (400 MHz, DMSO-d ) δ : 12.57 (s, 1H), 8.05 -
6 H
2
5

ACCEPTED MANUSCRIPT
8
.02 (m, 1H), 7.73 - 7.70 (m, 1H), 7.62 - 7.58 (m, 2H), 7.48 - 7.40 (m, 2H), 7.24 (d, J = 16.4
1
3
Hz, 1H), 7.21 - 7.13 (m, 2H); C NMR (75 MHz, DMSO-d ) δ : 151.1, 144.4, 135.5, 134.9,
6
C
1
33.4, 132.3, 129.4, 123.1, 122.3, 122.1, 119.2, 119.1, 111.6; LC-MS calcd.m/z 317, found
+
3
18 [(M+1)] .
3
2
(
E)-2-(2-(naphthalen-1-yl)vinyl)-1H-benzo[d]imidazole 4s: Off white solid (0.216g,
8
1
1
8
7
1
0%); M.pt.108-110 ⁰C; R = 0.38 (hexane/ethylacetate 7:3); [Found: C, 84.38; H, 5.15; N,
f
-1
0.31. C H N requires C, 84.42; H, 5.22; N, 10.36]; IR (ATR KBr cell, cm ) 3330, 3140,
1
9
14
2
1
581, 1340; H NMR (400 MHz, DMSO-d ) δ : 12.78 (s, 1H), 8.49 (d, J = 16.4 Hz, 1H),
6
H
.41 (d, J = 8.4 Hz, 1H), 8.08 - 7.95 (m, 3H), 7.68 - 7.57 (m, 5H), 7.30 (d, J = 16 Hz, 1H),
1
3
.20 (s, 2H); C NMR (75 MHz, DMSO-d ) δ : 151.3, 133.4, 133.0, 131.4, 131.0, 128.7,
6
C
28.3, 126.0, 125.7, 125.3, 123.4, 122.2, 119.6, 114.7; LC-MS calcd.m/z 270, found 271
+
[
(M+1)] .
(E)-2-(2-(anthracen-9-yl)vinyl)-1H-benzo[d]imidazole 4t: Yellow solid (0.216g, 79%);
M.pt.210-212 ⁰C; R = 0.50 (hexane/ethylacetate 7:3); [Found: C, 86.18; H, 5.00; N, 8.70.
f
-1
C H N requires C, 86.22; H, 5.03; N, 8.74]; IR (ATR KBr cell, cm ) 3470, 3168, 3041,
23
16
2
1
2
348, 1478; H NMR (400 MHz, DMSO-d ) δ : 12.96 (s, 1H), 8.64 (s, 1H), 8.58 (d, J = 16.4
6 H
Hz, 1H), 8.41 (d, J = 8 Hz, 2H), 8.17 (d, J = 7.2 Hz, 2H ), 7.63 - 7.57 (m, 6H), 7.25 - 7.23 (m,
1
3
2
1
3
H), 7.03 (d, J = 16.4 Hz, 1H); C NMR (100 MHz, DMSO-d ) δ : 151.0, 131.5, 131.0,
6 C
30.9, 129.4, 129.3, 127.7, 126.9, 126.8, 126.0, 125.7, 122.8; LC-MS calcd.m/z 320, found
+
21 [(M+1)] .
(E)-2-(2-(pyren-1-yl)vinyl)-1H-benzo[d]imidazole 4u: Brown solid (0.22g, 81%);
M.pt.186-188 ⁰C; R = 0.21 (hexane/ethylacetate 7:3); [Found: C, 87.12; H, 4.64; N, 8.10.
f
-1
C H N requires C, 87.18; H, 4.68; N, 8.13]; IR (ATR KBr cell, cm ) 3043, 2924, 2364,
25
16
2
1
1
1
2
3
1
741, 1629, 1433, 837, 738; H NMR (400 MHz, DMSO-d ) δ : 12.63 (s, 1H), 8.83 (d, J =
6 H
6.4 Hz, 1H), 8.75 (d, J = 9.2 Hz, 1H), 8.61 (d, J = 8 Hz, 1H), 8.34 - 8.33 (m, 4H), 8.22 (s,
H), 8.12 (t, J = 7.6 Hz, 1H), 7.63 (q, J = 3.2 Hz, 2H), 7.56 (d, J = 16.4 Hz, 1H), 7.24 (q, J =
1
3
.2 Hz, 2H); C NMR (100 MHz, DMSO-d ) δ : 151.8, 131.6, 131.5, 130.9, 130.8, 130.1,
6
C
28.8, 128.6, 128.3, 127.9, 127.0, 126.3, 126.0, 124.7, 124.5, 123.2, 122.8, 120.4; LC-MS
+
calcd.m/z 344, found 345 [(M+1)] .
(E)-2-(2-(furan-2-yl)vinyl)-1H-benzo[d]imidazole 4v: Off white solid (0.23g, 89%);
M.pt.236-238 ⁰C; R = 0.20 (hexane/ethylacetate 7:3); [Found: C, 74.22; H, 4.72; N, 13.30.
f
2
6

ACCEPTED MANUSCRIPT
-1
C H N O requires C, 74.27; H, 4.79; N, 13.33]; IR (ATR KBr cell, cm ), 3320, 1571,
13
10
2
1
1
3
480; H NMR (400 MHz, DMSO-d ) δ : 12.54 (s, 1H), 7.78 (s, 1H), 7.48 (d, J = 16 Hz,
6 H
1
3
H), 7.16 - 7.14 (m, 2H), 6.91 (d, J = 16 Hz, 1H), 6.76 (s, 1H), 6.60 (s, 1H); C NMR (75
MHz, DMSO-d ) δ : 152.0, 151.0, 144.7, 122.5, 122.3, 115.5, 112.9, 112.3; LC-MS
6
H
+
calcd.m/z 210, found 211 [(M+1)] .
E)-2-(2-(5-bromopyridin-3-yl)vinyl)-1H-benzo[d]imidazole 4w: Off white solid (0.224g,
(
8
1
1
2%); M.pt.268-270 ⁰C; R = 0.09 (hexane/ethylacetate 7:3); [Found: C, 56.00; H, 3.31; N,
f
-1
3.96. C H BrN : C, 56.02; H, 3.36; N, 14.00]; IR (ATR KBr cell, cm ) 3055, 2364, 1637,
14
10
3
1
550, 1429, 1020, 736; H NMR (400 MHz, DMSO-d ) δ : 12.67 (s, 1H), 8.80 (s, 1H), 8.64
6
H
(s, 1H), 8.45 (s, 1H), 7.64 - 7.60 (m, 2H), 7.49 (d, J = 7.6 Hz, 1H), 7.44 (d, J = 16.4 Hz, 1H),
13
7
.23 - 7.15 (m, 2H); C NMR (100 MHz, DMSO-d ) δ : 150.6, 150.2, 147.7, 136.0, 134.2,
6 C
+
1
29.6, 121.9, 121.2; LC-MS calcd.m/z 300, found 301 [(M+1)] .
(E)-2-(2-(thiophen-2-yl)vinyl)-1H-benzo[d]imidazole 4x: Off white solid (0.22g, 84%);
M.pt.225-226 ⁰C; R = 0.24 (hexane/ethylacetate 7:3); [Found: C, 68.98; H, 4.40; N, 12.35.
f
-1
1
C H N S: C, 69.00; H, 4.45; N, 12.38]; IR (ATR KBr cell, cm ) 3310, 3025,1545; H
13
10
2
NMR (400 MHz, DMSO-d ) δ : 12.52 (s, 1H), 7.76 (s, 1H), 7.64 (d, J = 16.4 Hz, 2H), 7.53
6
H
1
3
(
s, 2H), 7.50 - 7.37 (m, 2H), 7.18 - 7.09 (m, 2H), 7.03 (d, J = 16.4 Hz, 1H); C NMR (75
MHz, DMSO-d ) δ : 150.7, 140.9, 133.3, 132.8, 128.2, 122.9, 121.7, 119.3, 111.1; UPLC-
6
C
+
MS calcd.m/z 226, found 227 [(M+1)] .
(E)-2-(2-(5-bromothiophen-2-yl)vinyl)-1H-benzo[d]imidazole 4y: Off white solid (0.23g,
8
9
2
1
2
1
6%); M.pt.190-192 ⁰C; R = 0.31 (hexane/ethylacetate 7:3); [Found: C, 51.12; H, 2.92; N,
f
-1
.15. C H BrN S requires C, 51.16; H, 2.97; N, 9.18]; IR (ATR KBr cell, cm ) 3057, 2922,
1
3
9
2
1
365, 1645, 1427, 968, 738; H NMR (400 MHz, DMSO-d ) δ : 12.54 (s, 1H), 7.72 (d, J =
6
H
6 Hz, 1H), 7.56 (d, J = 7.2 Hz, 1H), 7.45 (d, J = 6.8 Hz, 1H), 7.25 (dd, J = 3.6 Hz, 8.8 Hz
13
H), 7.16 (s, 2H), 6.85 (d, J = 16 Hz, 1H); C NMR (75 MHz, DMSO-d ) δ : 150.0, 142.4,
6
C
38.6, 130.2, 127.7, 126.3, 121.8, 116.3, 114.3, 112.2; LC-MS calcd.m/z 305, found 306
+
[
(M+1)] .
General procedure for the preparation of 2-(2-(methylthio)-2-arylethyl)-1H-
benzo[d]imidazole (5a-y)
2
7

ACCEPTED MANUSCRIPT
To a solution of 1,1-bis(methylthio)-5-arylpenta-1,4-dien-3-one (1mol), glacial acetic acid
(3mL), was added 1,2-phenylenediamine (1mol) in one portion at room temperature . The
reaction mixture was stirred magnetically reflux at 110 ºC for 15h. The reaction mixture was
subsequently quenched with saturated aqueous NaHCO (20ml). The extracts were combined
3
washed with water, brine and then dried over anhydrous Na SO . The solvent was removed
2
4
under vacuum to afford the crude product which was then subjected to column
chromatography (silica gel) using ethyl acetate/Petroleum ether mixture as a gradient eluent
to furnish pure product (5a-y).
2
-(2-(methylthio)-2-phenylethyl)-1H-benzo[d]imidazole 5a: Off white solid, (0.24g, 75%);
M.pt.155-157 ⁰C; R = 0.25 (hexane/ethylacetate 7:3); [Found: C, 71.59; H, 5.98; N, 10.41.
f
-1
C H N S requires C, 71.61.37; H, 6.01; N, 10.44]; IR (ATR KBr cell, cm ) 3400, 2225,
16
16
2
1
1
599, 1450, 670; H NMR (300 MHz, CDCl ) δ : 7.52 (s, 1H), 7.34 - 7.26 (m, 5H), 7.24 -
3 H
1
3
7
.21 (m, 2H), 4.24 (t, J = 7.5 Hz, 1H), 3.48 (d, J = 8.4 Hz, 2H), 1.95 (s, 3H); C NMR (75
MHz, DMSO-d ) δ : 152.2, 141.0, 128.7, 127.5, 127.4, 122.3, 50.1, 36.2, 14.5; LC-MS
6
C
+
calcd.m/z 268, found 269 [(M+1)] .
2
-(2-(2-methoxyphenyl)-2-(methylthio)ethyl)-1H-benzo[d]imidazole 5b: Off white solid
(
0.22g, 72%); M.pt.154-156 ⁰C; R = 0.20 (hexane/ethylacetate 7:3); [Found: C, 68.40; H,
f
-
1
6
3
7
-
.05; N, 9.37. C H N OS requires C, 68.42; H, 6.08; N, 9.39]; IR (ATR KBr cell, cm )
17 18 2
1
020, 2360, 1598, 1502, 1400, 1198, 728; H NMR (400 MHz, DMSO-d ) δ : 12.28 (s, 1H),
6
H
.46 (s, 2H), 7.40 (dd, J = 1.6 Hz, 7.6 Hz, 1H), 7.25 - 7.18 (m, 1H), 7.13 - 7.08 (m, 2H), 6.99
1
3
6.93 (m, 2H), 4.85 (t, J = 7.6 Hz, 1H), 3.79 (s, 3H), 3.46 - 3.34 (m, 2H), 1.87 (s, 3H); C
NMR (100MHz, DMSO-d ) δ : 157.5, 156.9, 153.1, 151.8, 130.6, 129.6, 129.5, 128.6, 127.6,
6
C
1
2
24.7, 121.6, 121.3, 120.8, 112.1, 111.7, 56.1, 41.9, 34.3, 13.7; LC-MS calcd.m/z 298, found
+
99 [(M+1)] .
2
-(2-(3-methoxyphenyl)-2-(methylthio)ethyl)-1H-benzo[d]imidazole 5c: Off white solid;
(
0.217g, 68%); M.pt.160-162 ⁰C; R = 0.18 (hexane/ethylacetate 7:3); [Found: C, 68.37; H,
f
-
1
6
3
7
1
.04; N, 9.35. C H N OS requires C, 68.42; H, 6.08; N, 9.39]; IR (ATR KBr cell, cm )
17 18 2
1
053, 2366, 1645, 1589, 1417, 1269, 740; H NMR (400 MHz, DMSO-d ) δ ; 12.24 (s, 1H),
6
H
.44 (s, 2H), 7.22 - 7.02 (m, 1H), 7.10 - 7.07 (m, 2H), 6.94 - 6.91 (m, 2H), 6.78 - 6.76 (m,
1
3
H), 4.43 (t, J = 8 Hz, 1H), 3.69 (s, 3H), 3.38 - 3.33 (m, 2H), 1.88 (s, 3H); C NMR (100
2
8

ACCEPTED MANUSCRIPT
MHz, DMSO-d ) δ : 159.6, 152.7, 143.4, 129.8, 121.7, 120.3, 113.8, 112.8, 55.4, 49.1, 35.7,
6
C
+
1
4.2; LC-MS calcd.m/z 298, found 299 [(M+1)] .
2
-(2-(3-chlorophenyl)-2-(methylthio)ethyl)-1H-benzo[d]imidazole 5e: Off white solid
(
0.22g, 69%); M.pt.164-166 ⁰C; R = 0.28 (hexane/ethylacetate 7:3); [Found: C, 63.44; H,
f
-
1
4
3
7
.93; N, 9.20. C H ClN S requires C, 63.46; H, 4.99; N, 9.25]; IR (ATR KBr cell, cm )
16 15 2
1
053. 2350, 1589, 1487, 1200, 742; H NMR (400 MHz, DMSO-d ) δ : 12.24 (s, 1H), 7.46 -
6
H
.43 (m, 3H), 7.33 - 7.31 (m, 2H), 7.28 - 7.25 (m, 1H), 7.10 - 7.08 (m, 2H), 4.48 (t, J = 8.0
13
Hz, 1H), 3.40 (d, J = 7.2 Hz, 2H), 1.89 (s, 3H); C NMR (100 MHz, DMSO-d ) δ : 152.4,
6
C
1
3
44.4, 133.4, 130.6, 127.9, 127.6, 126.9, 121.8, 115.1, 48.4, 35.0, 14.9; LC-MS calcd.m/z
+
02, found 303 [(M+1)] .
2
-(2-(4-chlorophenyl)-2-(methylthio)ethyl)-1H-benzo[d]imidazole 5f: Off white solid
(
0.226g, 71%); M.pt.158-160 ⁰C; R = 0.26 (hexane/ethylacetate 7:3);. [Found: C, 63.39; H,
f
-1
4
.93; N, 9.19. C H ClN S requires C, 63.46; H, 4.99; N, 9.25]; IR (ATR KBr cell, cm )
16 15 2
1
3
044, 2300, 1460, 1298, 728; H NMR (400 MHz, DMSO-d ) δ : 12.22 (s, 1H), 7.43 - 7.33
6
H
1
3
(
m, 6H), 7.10 - 7.07 (m, 2H), 4.47 (t, J = 8.0 Hz, 1H), 3.43 - 3.32 (m, 2H), 1.88 (s, 3H); C
NMR (100 MHz, DMSO-d ) δ : 152.5, 140.8, 132.0, 130.0, 128.8, 122.0, 118.7, 111.3, 48.3,
6
C
+
3
5.2, 14.1; LC-MS calcd.m/z 302, found 303 [(M+1)] .
2
-(2-(2-fluorophenyl)-2-(methylthio)ethyl)-1H-benzo[d]imidazole 5g: Off white solid
(
0.236g, 74%); M.pt.126-128 ⁰C; R = 0.25 (hexane/ethylacetate 7:3); [Found: C, 67.08; H,
f
-
1
5
3
2
3
1
1
.24; N, 9.73. C H FN S requires C, 67.11; H, 5.28; N, 9.78]; IR (ATR KBr cell, cm )
16 15 2
1
042, 1700, 1425, 724; H NMR (400 MHz, DMSO-d ) δ : 12.30 (s, 1H), 7.54 - 7.50 (m,
6
H
H), 7.41 (d, J = 7.6 Hz, 1H), 7.32 - 7.25 (m, 1H), 7.20 - 7.07 (m, 4H), 4.75 (t, J = 8 Hz, 1H),
13
.52 - 3.42 (m, 2H), 1.95 (s, 3H); C NMR (100 MHz, DMSO-d ) δ : 161.5, 159.1, 152.5,
6
C
43.7, 134.6, 129.5, 129.4, 129.3, 128.6, 128.5, 124.9, 122.0, 121.4, 118.7, 116.0, 115.8,
+
11.3, 41.9, 34.0, 13.9; LC-MS calcd.m/z 286, found 287 [(M+1)] .
2
-(2-(3-fluorophenyl)-2-(methylthio)ethyl)-1H-benzo[d]imidazole 5h: Off white solid
(
0.230g, 72%); M.pt.142-144 ⁰C; R = 0.21 (hexane/ethylacetate 7:3); [Found: C, 67.06; H,
f
-
1
5
3
2
8
.26; N, 9.72. C H FN S requires C, 67.11; H, 5.28; N, 9.78]; IR (ATR KBr cell, cm )
16 15 2
1
315, 2364, 1417, 1155, 740; H NMR (400 MHz, DMSO-d ): δ : 12.22 (s, 1H), 7.47 (s,
6
H
H), 7.34 (q, J = 8 Hz, 1H), 7.19 (t, J = 7.6 Hz, 2H), 7.10 - 7.08 (m, 2H), 7.04 (td, J = 2 Hz,
1
3
.4 Hz, 1H), 4.49 (t, J = 8 Hz, 1H), 3.43 - 3.37 (m, 2H), 1.89 (s, 3H); C NMR (100 MHz,
2
9