Iodine-mediated C-N and C-S bond formation: regioselective synthesis of benzo[4,5]imidazo[2,1-b]thiazoles

Article abstract of DOI:10.1039/C6NJ02102F

A new strategy involving iodine-mediated reactions for the construction of C-N and C-S bonds has been reported. This method is base and metal free and features inexpensive catalysts, with a simple procedure and a short reaction time.

Full text of DOI:10.1039/C6NJ02102F

View Article Online
View Journal
NJC
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: S. Ambethkar, M.
Vellimalai, V. Padmini and N. Bhuvanesh, New J. Chem., 2016, DOI: 10.1039/C6NJ02102F.
This is an Accepted Manuscript, which has been through the
Volume 40 Number
1 January 2016 Pages 1–846
Royal Society of Chemistry peer review process and has been
accepted for publication.
NJC
Accepted Manuscripts are published online shortly after
New Journal of Chemistry
www.rsc.org/njc
A journal for new directions in chemistry
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
rsc.li/njc

Please do not adjust margins
New Journal of Chemistry
Page 1 of 7
View Article Online
DOI: 10.1039/C6NJ02102F
ARTICLE
Iodine -Mediated C-N and C-S bond formation: Regioselective
synthesis of benzo [4,5]imidazo[2,1-b] thiazoles.
Sethurajan Ambethkara, Muthalu Vellimalaib, Vediappen Padminia* and Nattamai Bhuvaneshc
Received 00th January 20xx,
Accepted 00th January 20xx
The development of new strategy involving iodine mediated reaction for the construction of C-N and C-S bond formation
has been reported. This method features inexpensive catalyst, base free and metal free with simple procedure and short
reaction time.
DOI: 10.1039/x0xx00000x
www.rsc.org/
reactions (scheme 1). Recently Gabriele20 et al reported
palladium-catalyzed carbonylative multicomponent synthesis
of functionalized benzimidazothiazoles.
Introduction
The Oxidative C-H bond activation/functionalization has
emerged as an effective tool for the construction of carbon-
carbon and carbon-heteroatom bond formations by using
transition metals as a catalyst.1-2 Also there are metal free
organic synthesis for the construction C-C and C-X bond
formations are popular.3 Iodine seems to be an excellent
reagent owing to its characteristics such as ready availability,
low cost and non-metallic nature. Moreover, molecular iodine
has additional advantages as it has a lowest dissociation, no
radioactivity and moderate redox potential.4 The use of iodine
in oxidative coupling reactions has been extensively explored.
Specifically, molecular iodine has been extensively used for C-
S5 coupling reaction involving sulfonylating reagents such as
DMSO, R-SO2NHNH2, R’SO2Na and R2S2. Li et al.6 reported
iodine-mediated intramolecular cyclization of enamines via
iodide intermediates.
HO
N
S
B
S
N
O
N
N
NH
NH
Cl
F
A
S
N
N
S
NH
CH3
N
N
D
C
Figure 1. The representative examples of biological active imidazothiazoles.
Benzimidazo[2,1-b]thiazoles
are
privileged
structures
However, there is no report available for the synthesis of
benzimidazothiazoles starting from enamines. Enaminones are
versatile synthons for organic synthesis and their chemistry
received much attention in recent years. They are ambient in
nature having the nucleophilicity of enamine and
electrophilicity of enone finding applications as building blocks
for the construction of large number of organic compounds.21
Thus enaminones has been chosen as the starting material for
the present investigation to get benzimidazothiazoles. The
enamino ketones, (E)-1-(4-aryl)-3-(dimethylamino)-prop-2-en-
1-ones, required for the present work, were prepared by the
reported methods.22 To the best of our knowledge, this is the
first report for the simultaneous construction of C-N and C-S
bonds in a single operation using molecular iodine (scheme 2).
encountered in wide range of natural products and bioactive
molecules. This class of compounds exhibits diverse biological
activities such as antibacterial,7 antitumor,8 antidiabetic,9 anti-
inflammatory,10 antitubercular,11 anti-cardiovascular agents,12
anti-neurodegenerative13 and immunosuppressive activities.14
A number of synthetic methods have been developed for the
synthesis of benzimidazo[2,1-b]thiazoles including copper (I)
catalyzed arylation,15 Pd–Cu catalyzed heterocyclization16 and
carbene rearrangement of hypervalent bromanes.17 During
2010 Chen18 et al. developed a powerful copper (I) catalysed
aminothiolation of 1,1-dihaloalkene and later, in 2012, Xiao19
et al. established a new method for the synthesis of N-fused
heterocycles via C-S coupling and 5-endo-dig cyclization
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 2 of 7
View Article Online
DOI: 10.1039/C6NJ02102F
ARTICLE
Journal Name
Next we tried different oxidants such as K2S2O8 (1.0 equiv) and
oxone (1.0 equiv) in CH3CN at room temperature, but
unfortunately the desired product is not formed (Table 1,
entry 10 and 11). With equimolar amount of iodine (Table 1,
entries 12-18), this reaction worked well in acetic acid and
acetonitrile, but not effective in other solvents such as
toluene, dichloromethane, THF, DMF and ethanol. By simply
stirring
1 and 2a with iodine (1.0 equiv) in acetic acid at room
temperature under open air for 2 h, the product was obtained
in 92% yield (Table 1, entry 14). When the reaction was carried
out with and without oxygen atmospheres, the yield of the
reaction in absence of air atmosphere was apparently lower,
which proved that O2 air played an energetic role in the
process. These optimized results indicate that one equivalent
of iodine is necessary for the full conversion of the starting
materials. When I2 (0.5 equiv) was used, only 47% product was
obtained even after 6 h (Table 1, entry 19).
Scheme1. Previous approaches for the Synthesis of Imidazo [2,1-b]thiazoles.
Table 1. Optimization of reaction conditions[a]
Entry
Promoter
Solvent
Temp
Time
Yield (%)[b]
(1.0 equiv)
----[c]
Scheme 2. Preparation of benzo[4,5]imidazo[2,1-b]thiazol-3-
yl(phenyl)methanone.
1
2
AcOH
AcOH
AcOH
DMF
RT
RT
6 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
6 h
NR[d]
62
57
51
20
25
NR
40
48
NR
NR
31
55
92
81
62
58
38
47
CuI
Results and discussion
3
CuI
100 ◦C
100 ◦C
100 ◦C
100 ◦C
100 ◦C
100 ◦C
RT
In continuation of our ongoing research for the
development of new routes to access heterocyclic
systems,23 we started our investigation by employing of 2-
4
CuI
5
CuCl
CuBr
CuO
Cu(OTf)2
Cu(OAc)2
K2S2O8
Oxone[e]
I2
DMF
6
DMF
mercaptobenzimidazole
1(1.0 equiv), and (E)-1-(4-aryl)-3-
(dimethylamino)-prop-2-en-1-one 2a(1.0 equiv),as model
substrates for the synthesis of benzo[4,5]imidazo[2,1-
b]thiazole (SA-1) under various reaction conditions as
depicted in Table 1. When the reaction was carried out in 5
mL of acetic acid at room temperature for 6 h, no product
was formed (Table 1, entry 1). Further optimization
revealed that the use of CuI (1.0 equiv) as a promoter in
acetic acid at room temperature under open air for 12 h
yielded 62% of the product (Table 1, entry 2). Here we
expected SA'-1 as a product, because sulphur is strong
nucleophile than nitrogen in 2-mercaptobenzimidazole, it
can undergo thione-thiol tautomerization. There could be
nucleophilic attack of (E)-3-(dimethylamino)-1-phenylprop-
2-en-1-one with 1H-benzo[d]imidazole-2-thiol led to
elimination of N,N-dimethylamine and then intramolecular
cyclization may afford expected product SA'-1. Unfortunately
the expected product SA'-1 was not formed. The product was
unexpected SA-1 formed via nucleophilic substitution reaction
and intramolecular oxidative cyclization followed by
elimination of Me2NH as a by-product was shown in scheme 2.
The structure of SA-1 was undoubtedly assigned by spectral
and single crystal X-ray data (Figures 2 and 3). Next we
optimized equimolar amounts various copper reagents such as
CuI, CuCl, CuBr, CuO, Cu(OTf)2 and Cu(OAc)2 as a promoter in
acetic acid and DMF under atmospheric air. They were found
to be less effective for this transformation (Table 1, entry 3-9).
7
DMF
8
DMF
9
DMF
10
11
12
13
14
15
16
17
18
19
MeCN
MeCN
Toluene
DCM
RT
RT
RT
I2
RT
6 h
I2
AcOH
MeCN
DMF
RT
2 h
I2
RT
2 h
I2
RT
6 h
I2
THF
RT
6 h
I2
EtOH
AcOH
RT
6 h
I2 (0.5)
RT
6 h
aReaction conditions: 2-mercaptobenzimidazole (1.0 equiv), (E)-1-(4-aryl)-3-
(dimethylamino)-prop-2-en-1-one 2 (1.0 equiv), promoter(1.0equiv) oxidant (1.0
equiv) under open air in 5 mL of solvent. bIsolated yield. cReagent free reaction.
dNo reaction. eChemical formula of oxone is 2KHSO5·KHSO4·K2SO4.
With the optimized conditions in hand, we extended the scope
of the reaction using electron withdrawing and electron
donating substituent in phenyl rings were converted to the
corresponding products in moderate to good yields (Scheme 2,
78–92%; SA-1-14). The optimized conditions were also
successfully applied to a hetero aryl enaminones, which
generated the corresponding heterocyclic substituted products
in moderate yields (71 and 77%; SA-15 and 16) respectively. In
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 3 of 7
View Article Online
DOI: 10.1039/C6NJ02102F
Journal Name
ARTICLE
HI
order to understand the mechanism of this reaction, the
radical trapping experiments were tested (Scheme 3). TEMPO
O
(2,2,6,6-tetramethylpiperidinooxy) was used as
a radical
H
R
O
I
H
N
scavenger. In the presence of TEMPO, SA-1 was observed in
good yield (89%) and this result indicating that radical
intermediates were not involved in this reaction.24
SH
S
N
R
N
HN
HN
N
A
HI
B
1A
Table 2. Synthesized compounds SA-1-16a
I2
H
N
S
O
2
O
O
O
N
N
H
S
O
S
S
N
S
N
N
N
O
R
1
N
H
N
N
N
N
O2
N
Cl
R
S
N
SA-4 83 %
SA-3 90 %
SA-1 92 %
SA-2 78 %
O
N
C
O
S
O
N
S
S
O
O
N
N
S
N
N
N
N
N
Br
N
R
S
N
F
Br
SA-8 86 %
SA-5 89 %
SA-6 88 %
SA-7 84 %
SA-1
HN
O
O
S
N
O
O
S
S
O
S
Scheme 4. Proposed mechanism for the formation of benzo[4,5]imidazo[2,1-
b
N
N
N
N
N
N
N
]thiazol-3-yl(phenyl)methanone.
O
SA-9 81 %
SA-10 83 %
O
SA-12 79 %
SA-11 85 %
O
S
O
O
S
N
N
S
N
SA-15 71 %
S
N
O
N
N
N
N
Cl
S
S
O
Cl
Br
SA-13 84 %
SA-14 87 %
SA-16 77 %
aIsolated yield
.
Figure 2. ORTEP diagram of SA-2.
O
O
H
N
I2, AcOH
N
S
N
S
TEMPO
RT
N
N
H
89 %
2a
SA-1
1
Scheme 3 Control experiments
.
The structures of all the synthesized compounds were confirmed by
1H NMR, 13C NMR, ESI-MASS and HRMS spectroscopic methods. The
structures of compounds SA-2 and SA-6 were undoubtedly
confirmed by X-ray diffraction analysis.25 On the basis above results
and literature report, a tentative mechanism is proposed for the
formation of benzo[4,5]imidazo[2,1-b]thiazole (SA-1-16) as depicted
in scheme 4. Initially the addition reaction between enaminones 2
and iodine leads to the formation of intermediate A.26 The
tautomeric thiol 1A under acidic conditions undergoes nucleophilic
substitution reaction affording intermediate B by the removal of HI
molecule. This is followed by an intramolecular cyclization giving C
and finally the removal of N,N-dimethylamine under acidic
condition leads to the formation of the desired product
benzo[4,5]imidazo[2,1-b]thiazole.
Figure 3. ORTEP diagram of SA-6.
Conclusions
We have developed a mild, novel and efficient iodine-mediated
oxidative C-N and C-S bond reaction for the synthesis of substituted
benzo[4,5]imidazo[2,1-b]thiazoles. The reaction is highly selective,
metal and base free and shorter reaction time.
Experimental section
General methods
The melting points were measured in open capillary tubes and
1
are uncorrected. The H and 13C NMR spectra were recorded
on a Bruker (Avance) 300 MHz NMR instrument using TMS as
internal standard either CDCl3 or DMSO-d6 as solvent.
Chemical shifts are given in parts per million (δ-scale) and the
coupling constants are given in hertz (Hz). Silica gel-G plates
(Merck) were used for thin layer chromatography (TLC)
analysis with a mixture of petroleum ether (60-80 °C) and ethyl
acetate as eluent. The single crystal X-ray data were collected
on BRUKER GADDS X-ray (three-circle) diffractometer with Mo
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 4 of 7
View Article Online
DOI: 10.1039/C6NJ02102F
ARTICLE
Journal Name
313.18 (M+1)+. Anal.Calcd for C16H9ClN2OS: C, 61.44; H, 2.90; N,
8.96; found C, 61.41; H, 2.88; N, 8.93.
Ka(k= 1.5418 A˚) radiation. Elemental analyses were
performed on a vario EL III CHNS elemental analyzer. Mass
spectra were recorded in LCQ Fleet mass spectrometer,
Thermo Fisher Instruments Limited, US. Electrospray ionization
mass spectrometry (ESI-MS) analysis was performed in the
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(4-bromophenyl)methanone
(SA-5) White solid, mp; 208-10 °C; 1H NMR (300 MHz, CDCl3) δ: 8.64
(s, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.62 (d, J = 8.7 Hz, 2H), 7.56-7.52 (m,
3H), 7.24 (t, J = 8.1 Hz, 1H) 7.10 (t, J = 8.1 Hz, 1H) ppm; 13C NMR (75
MHz, CDCl3) δ: 185.6, 155.8, 147.2, 135.0, 131.7, 130.0, 129.2,
129.0, 127.4, 127.2, 124.7, 121.7, 118.5, 111.5 ppm. MS m/z 357.0
(M+1)+. Anal.Calcd for C16H9BrN2OS: C, 53.80; H, 2.54; N, 7.54;
found C, 53.77; H, 2.51; N, 7.51.
positive ion and negative ion mode on
chromatography ion trap.
a
liquid
General experimental procedure for benzo[4,5]imidazo[2,1-
b]thiazol-3-yl(phenyl)methanone SA-1-16. A mixture of 2-
mercaptobenzimidazole
1
(1.0 equiv), (E)-1-(4-aryl)-3-
(dimethylamino)-prop-2-en-1-one 2 (1.0 equiv), and iodine
(1.0equiv) was added to 5 mL of acetic acid under open air at
room temperature for 2 h. The completion of the reaction was
monitored by TLC. After completion of the reaction, the
reaction mixture was poured into water and workup with
sodium thiosulfate and the solution was extracted with ethyl
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(4-flurophenyl)methanone
(SA-6) White solid, mp; 180-82°C; 1H NMR (300 MHz, CDCl3) δ: 8.43
(s, 1H), 7.42-7.38 (m, 3H), 7.07 (d, J = 7.8 Hz, 1H) 6.79 (t, J = 7.8 Hz,
1H), 6.75 - 6.66 (m, 3H) ppm; 13C NMR (75 MHz, CDCl3) δ: 184.2,
1
3
164.1 (d, JC-F =251.8 Hz), 155.0, 146.8, 131.9, 130.4 (d, JC-F = 9 Hz),
2
acetate. The combined organic phase was dried over Na2SO4 128.7, 127.9, 126.8, 123.7, 120.7, 117.6, 114.8 (d, JC-F = 21.8 Hz),
111.1 ppm. MS m/z 297.13 (M+1)+. Anal.Calcd for C16H9FN2OS: C,
and then the solvent was removed. The crude sample was
purified by column chromatography.
64.85; H, 3.06; N, 9.45; found C, 64.81; H, 3.03; N, 9.41.
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(phenyl)methanone
(SA-1)
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(3-bromophenyl)methanone
(SA-7) White solid, mp; 163-65 °C; 1H NMR (300 MHz, CDCl3) δ: 8.38
(s, 1H), 8.11(s, 1H), 7.91 (d, J = 7.8 Hz, 2H), 7.85 (d, J = 7.8 Hz, 1H),
7.60 - 7.55 (m, 2H), 7.45 (t, J = 7.5 Hz, 1H) ppm; 13C NMR (75 MHz,
CDCl3) δ: 185.6, 138.8, 136.0, 131.6, 130.7, 129.8, 127.2, 125.6,
125.5, 123.3, 122.4, 119.8, 111.1 ppm. MS m/z 358.98 (M+1)+.
Anal.Calcd for C16H9BrN2OS: C, 53.80; H, 2.54; N, 7.84; found C,
53.76; H, 2.51; N, 7.81.
White solid, mp; 142-44 °C; 1H NMR (300 MHz, CDCl3) δ: 8.22 (s,
1H), 7.86 (d, J = 8.1 Hz, 2H), 7.77 (d, J = 8.1 Hz, 1H), 7.67 (t, J = 7.5
Hz, 2H), 7.57 (t, J = 7.8 Hz, 2H), 7.41 (t, J = 7.2 Hz, 1H), 7.28 (t, J =
7.2 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ: 187.2, 156.7, 148.6,
137.0, 133.1, 130.0, 129.5, 129.0, 128.7, 125.1, 122.0, 122.0, 119.7,
110.8 ppm. MS m/z 279.1 (M+1)+. Anal.Calcd for C16H10N2O2S: C,
69.05; H, 3.62; N, 10.07; found C, 69.01; H, 3.59; N, 10.04.
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(p-tolyl)methanone
(SA-2)
[1,1'-biphenyl]-4-yl(benzo[4,5]imidazo[2,1-b]thiazol-2-
White solid, mp; 155-57 °C; 1H NMR (300 MHz, CDCl3) δ: 8.21 (s,
1H), 7.77 (d, J = 8.1 Hz, 3H), 7.64 (d, J = 8.1 Hz, 1H), 7.42-7.34 (m,
3H), 7.26 (t, J = 7.5 Hz, 1H), 2.47 (s, 3H) ppm; 13C NMR (75 MHz,
CDCl3) δ: 186.8, 156.7, 148.5, 144.0, 134.3, 130.2, 129.7, 128.8,
125.0, 121.9, 119.6, 110.7, 21.79 ppm. MS m/z 292.3560 (M)+.
Anal.Calcd for C17H12N2OS: C, 69.84; H, 4.14; N, 9.58; found C,
69.81; H, 4.11; N, 9.54.
yl)methanone (SA-8) Brown solid, mp; 157-59 °C; 1H NMR (300
MHz, CDCl3) δ: 8.41 (s, 1H), 8.07 (d, J = 7.8 Hz, 2H), 7.92-7.87 (m,
3H), 7.83-7.73 (m, 3H), 7.64-7.51 (m, 4H), 7.43 (t, J = 7.5 Hz, 1H)
ppm; 13C NMR (75 MHz, CDCl3) δ: 186.9, 157.3, 148.9, 146.3, 139.9,
136.0, 130.6, 129.6, 129.4, 129.4, 128.8, 127.9, 127.6, 127.6, 125.4,
122.3, 120.0, 111.1 ppm. MS m/z 353.07 (M-1)-.Anal.Calcd for
C
22H14N2OS: C, 74.55; H, 3.98; N, 7.90; found C, 74.52; H, 3.95; N,
7.87.
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(nitrophenyl)methanone (SA-
1
3) Yellow solid, mp; 190-92 °C; H NMR (300 MHz, CDCl3) δ: 8.73 (s,
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(naphthalen-1-yl)methanone
(SA-9) White solid, mp; 203-05 °C; 1H NMR (300 MHz, CDCl3) δ: 8.17
(s, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.95-7.93 (m, 1H), 7.83 (t, J = 7.5 Hz,
2H), 7.66 (m, 4H), 7.46 (t, J = 7.5 Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H)
ppm; 13C NMR (75 MHz, CDCl3) δ: 188.2, 134.4, 134.0, 133.0, 132.3,
130.4, 129.1, 128.6, 128.0, 127.3, 127.1, 126.6, 125.8, 125.1, 124.4,
122.7, 119.0, 111.2 ppm. MS m/z 329.11 (M+1)+. Anal.Calcd for
C20H12N2OS: C, 73.15; H, 3.68; N, 8.53; found C, 73.12; H, 3.66; N,
8.50.
1H), 8.54 (d, J = 8.1 Hz, 2H), 8.28 (s, 1H), 8.23 (d, J = 8.1 Hz, 2H), 7.82
(m, 2H), 7.72 (d, J = 8.1 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H ), 7.34 (t, J =
7.8 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ: 185.6, 150.7, 128.5,
124.7, 123.3, 121.5, 120.1, 119.7, 117.6, 116.6, 114.2, 105.1, 104.6
ppm. MS m/z 323.03 (M+1)+. Anal.Calcd for C16H9N3O3S: C, 59.44; H,
2.81; N, 13.00; found C, 59.41; H, 2.78; N, 12.97.
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(4-chlorophenyl)methanone
(SA-4) White solid, mp; 177-79 °C; 1H NMR (300 MHz, CDCl3) δ: 8.25
(s, 1H), 7.83-7.63 (m, 3H), 7.68 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 7.5 Hz,
2H), 7.43 (t, J = 7.5 Hz, 1H), 7.30 (t, J = 7.5 Hz, 1H) ppm; 13C NMR (75
MHz, CDCl3) δ: 185.9, 156.6, 148.6, 139.5, 135.2, 130.0, 129.7,
129.5, 129.34, 125.4, 125.2, 122.1, 119.7, 110.8 ppm. MS m/z
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(naphthalen-2-yl)methanone
(SA-10) White solid, mp; 212-14 °C; 1H NMR (300 MHz, CDCl3) δ:
8.43 (s, 1H), 8.33 (s, 1H), 8.06-8.03 (m, 2H), 7.97 (t, J = 7.8 Hz, 1H),
7.84 (d, J = 7.8 Hz, 1H), 7.72-7.64 (m, 3H), 7.47 (t, J = 7.8 Hz, 1H),
7.31 (t, J = 7.8 Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H) ppm; 13C NMR (75
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 5 of 7
View Article Online
DOI: 10.1039/C6NJ02102F
Journal Name
ARTICLE
MHz, CDCl3) δ: 191.8, 161.2, 152.7, 140.1, 138.9, 137.2, 135.2, benzo[4,5]imidazo[2,1-b]thiazol-2-yl(5-bromothiophen-2-
134.5, 133.7, 133.5, 132.6, 132.0, 129.8, 129.5, 126.8, 123.6, 117.2 yl)methanone (SA-16) Yellow solid, mp; 178-80 °C; 1H NMR (300
ppm. MS m/z 329.09 (M+1)+. Anal.Calcd for C20H12N2OS: C, 73.15; H, MHz, CDCl3) δ: 8.47 (s, 1H), 8.89 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.1
3.68; N, 8.53; found C, 73.11; H, 3.65; N, 8.50.
Hz, 1H), 7.69 (d, J = 4.2 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.31 (t, J =
7.8 Hz, 1H ), 7.22 (d, J = 4.2 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3)
δ: 176.3, 156.3, 148.7, 142.9, 133.0, 131.6, 129.6, 128.5, 125.3,
123.8, 123.4, 122.2, 119.9, 110.9 ppm. MS m/z 364.9 (M+1)+.
Anal.Calcd for C14H7BrN2OS2: C, 46.29; H, 1.94; N, 7.71; found C,
46.26; H, 1.92; N, 7.68.
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(4-
methoxyphenyl)methanone (SA-11) White solid, mp; 161-63 °C; 1H
NMR (300 MHz, CDCl3) δ: 8.25 (s, 1H), 7.91(d, J = 8.4 Hz, 2H), 7.81
(d, J = 8.4 Hz, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.42 (t, J = 7.5 Hz, 1H),
7.06 (d, J = 8.4 Hz, 2H), 7.31 (t, J = 7.5 Hz, 1H), 3.92 (s, 3H) ppm; 13
C
Acknowledgements
NMR (75 MHz, CDCl3) δ:185.6, 163.7, 156.5, 148.4, 131.0, 130.2, S.A. is gratefully acknowledged for the Research Fellowship from
129.5, 124.9, 124.5, 121.9, 119.5, 114.2, 110.8, 55.6 ppm. MS m/z
309.13 (M+1)+. Anal.Calcd for C17H12N2O2S: C, 66.22; H, 3.92; N,
9.08; found C, 66.18; H, 3.89; N, 9.04.
UGC-RGNF. We thank the DST, New Delhi for assistance under the
IRHPA program for the NMR facility.
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(3-
Notes and references
methoxyphenyl)methanone (SA-12) White solid, mp; 170-72 °C; 1H
NMR (300 MHz, CDCl3) δ: 8.29 (s, 1H), 8.01 (s, 1H), 7.79 (d, J = 7.8
Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.44 (broad,
2H), 7.29 (t, J = 7.5 Hz, 1H), 6.99 (d, J = 7.8 Hz, 1H), 3.97 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3) δ:185.6, 153.6, 149.6, 130.0, 129.7,
125.0, 124.5, 123.2, 121.9, 119.7, 113.3, 110.7, 110.3, 56.2 ppm.
Anal.Calcd for C17H12N2O2S: C, 66.22; H, 3.92; N, 9.08; found C,
66.18; H, 3.89; N, 9.04.
1. (a) X. Chen, K. M. D. Engle, H. Wang, J. Q. Yu, Angew. Chem.,
Int. Ed. 2009, 48, 5094-5115; (b) C. L. Sun, B.J. Li, Z.J. Shi,
Chem. Commun. 2010, 46, 677-685; (c) P. B. Arockiam, C.
Bruneau, P. H. Dixneuf, Chem. Rev. 2012, 112, 5879-5918; (d)
S. A. Girard, T. Knauber, C.J. Li, Angew. Chem., Int. Ed. 2014,
53, 74-100; (e) J. Zhang, H. Chen, C. Lin, Z. Liu, C. Wang, Y.
Zhang. J. Am. Chem. Soc. 2015, 137, 12990−12996.
2. (a) X. X. Guo, D. W. Gu, Z. Wu, W. Zhang, Chem. Rev. 2015,
115, 1622-51; (b) D. H.Wang, K. M. Engle, B. F. Shi, J. Q Yu,
Science. 2010, 327, 315-19; (c) R. Giri, B. F. Shi, K. M. Engle,
N. Maugel, J. Q.Yu, Chem. Soc. Rev. 2009, 38, 3242-72; (d) J.
F. Hartwig, Chem. Soc. Rev. 2011, 40, 1992-2002; (e) C.
Zhang, C.Tang, N. Jiao, Chem. Soc. Rev. 2012, 41, 3464-3484;
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(3,4-
methoxyphenyl)methanone (SA-13) White solid, mp; 127-29 °C; 1H
NMR (300 MHz, CDCl3) δ: 8.29 (s, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.70
(d, J = 7.8 Hz, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.44 (broad, 2H), 7.29 (t, J
= 7.5 Hz, 1H), 6.99 (d, J = 7.8 Hz, 1H), 4.00 (s, 3H), 3.97 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3) δ:185.7, 156.8, 153.6, 149.7, 148.5,
130.1, 129.8, 129.6, 125.0, 124.5, 123.3, 122.0, 119.7, 111.3, 110.8,
110.3, 56.3, 56.3 ppm. MS m/z 339.30 (M+1)+. Anal.Calcd for
C18H14N2O3S: C, 63.89; H, 4.17; N, 8.28; found C, 63.86; H, 4.15; N,
8.25.
(f) G. Rouquet, N. Chatani, Angew. Chem., Int. Ed. 2013, 52
,
11726-11743; (g) J.W. Delord, T. Dro¨ge, F. Liu, F. Glorius,
Chem. Soc. Rev., 2011, 40, 4740-4761.
3. (a) R. K. Kumar, S. Manna, D. Mahesh, D. Sar, T.
Punniyamurthy, Asian. J. Org. Chem, 2013, 2, 843-847; (b) Y.
Chi, W. X. Zhang, Z. Feng, Org. Lett. 2014, 16, 6274-6277; (c)
M. A. Omar, W. Frey, J. Conrad, U. J. Beifuss, J. Org. Chem.,
2014, 79, 10367-10377; . (d) W. Zhao, P. Xie, Z. Bian, A. Zhou,
H. Ge, M. Zhang, Y. Ding, L. Zheng, J. Org. Chem., 2015, 80
9167–9175; (e) W. Yu, Y. Du, K. Zhao, Org. Lett., 2009, 11
2417-2420.
,
,
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(3,4-
4. (a) M. Lamani, K. R. Prabhu, J. Org. Chem. 2011, 76, 7938-
7944; (b) X. Wu, Q. Gao, S. Liu, A. Wu, Org. Lett., 2014, 16
dichlorophenyl)methanone (SA-14) Yellow solid, mp; 127-29 °C; 1H
NMR (300 MHz, CDCl3) δ: 8.26 (s, 1H), 7.96 (s, 1H), 7.80 (d, J = 8.1
Hz, 1H), 7.72 - 7.64 (m, 3H), 7.46 (t, J = 7.5 Hz, 1H), 7.34 (t, J = 7.5
Hz, 1H ), ppm; 13C NMR (75 MHz, CDCl3) δ: 184.7, 156.6, 148.8,
137.8, 136.7, 133.9, 131.2, 130.6, 129.6, 129.4, 127.7, 125.6, 125.4,
122.3, 120.0, 110.9 ppm. Anal.Calcd for C16H8Cl2N2OS: C, 55.35; H,
2.32; N, 8.07; found C, 55.31; H, 2.30; N, 8.04.
,
4582–4585; (c) Y. Xie, J. Wu, X. Che, Y. Chen, H. Huang, G. J.
Deng, Green Chem., 2016,18, 667-671.
5. (a) X. Kang, R. Yan, G. Yu, X. Pang, X. Liu, X. Li, L. Xiang, G.
Huang, J. Org. Chem., 2014, 79, 10605–10610; (b) X. Zhao, T.
Li, L. Zhang, K. Lu, Org. Biomol. Chem., 2016,14, 1131-1137.
6. Z. He, H. Li, Z. Li, J. Org. Chem. 2010,75,4636–4639.
7. M. Palkar, M. Noolvi, R. Sankangoud, V. Maddi, Arch.
Pharm.Chem. Life Sci., 2010, 343, 353-359.
8. (a) A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, J. Med.
Chem., 2008, 51, 7508-7513; (b) A. Furlan, F. Colombo, A.
Kover, N. Issaly, Eur. J. Med. Chem., 2012, 47, 239-247; (c) J.
H. Park, M. I. El-Gamal, Y.S. Lee, G. H. Oh, Eur. J. Med. Chem.
2011, 46, 5769-5777; (d) T. U. Mayer, T. M. Kapoor, S. J.
Haggarty, R. W. King, S. L. Schreiber, T. J. Mitchison, Science,
1999, 286,971-974.
9. C. B. Vu, J. E. Bemis, J. S. Disch, P. Y. Ng, J.J. Nunes, J. C.
Milne, D. P. Carney, A. V. Lynch, J. J. Smith, S. Lavu, P. D.
Lambert, D. J. Gagne, M. R. Jirousek, S. Schenk, J. M. Olefsky,
R. B. Perni, J. Med. Chem. 2009, 52, 1275–1283.
benzo[4,5]imidazo[2,1-b]thiazol-2-yl(thiophen-2-yl)methanone
(SA-15) Yellow solid, mp; 185-87 °C; 1H NMR (300 MHz, CDCl3) δ:
8.52 (s, 1H), 7.96 (d, J = 3.9 Hz, 1H), 7.80 (t, J = 8.1 Hz, 2H), 7.74 (d, J
= 7.8 Hz,1H), 7.44 (t, J = 7.8 Hz,1H ), 7.35 (t, J = 7.8 Hz,1H ), 7.28(m,
1H) ppm; 13C NMR (75 MHz, CDCl3) δ: 177.6, 156.5, 148.6, 141.3,
134.2, 132.9, 129.6, 129.3, 128.5, 125.1, 123.8, 122.1, 119.7, 110.9
ppm. MS m/z 285.0 (M+1)+. Anal.Calcd for C14H8N2OS2: C, 62.85; H,
3.23; N, 8.93; found C, 62.82; H, 3.20; N, 8.90.
10. B. Tozkoparan, M. Ertan, P. Kelicen, R. Demirdamar,
Farmaco, 1999, 54, 588-593.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 6 of 7
View Article Online
DOI: 10.1039/C6NJ02102F
ARTICLE
Journal Name
11. G. C. Moraski, L. D. Markley, M. Chang, S. Cho, S. G.
Franzblau, C. H. Hwang, H. Boshoff, M. Miller, J. Bioorg. Med.
Chem. 2012, 20, 2214-2220.
12. A. Locatelli, S. Cosconati, M. Micucci, A. Leoni, L. Marinelli, A.
Bedini, P. Loan, S.M. Spampinato, E. Novellino, A. Chiarini, R.
Budriesi, J. Med. Chem. 2013, 56, 3866-3877.
13. N. Pietrancosta, A. Moumen, R. Dono, P. Lingor, V.
Planchamp, F. Lamballe, M. Bahr, J. L. Kraus, F. Maina, J.
Med. Chem., 2006, 49, 3645-3652.
14. T. Mase, H. Arima, K. Tomioka, T.Yamada, K. Murase, J. Med.
Chem, 1986, 29, 386-394.
15. G. Huang, H. Sun, X. Qiu, C. Jin, C. Lin, Y. Shen, J. Jiang, L.
Wang, Org. Lett., 2011, 13, 19, 5224-5227.
16. M. M. Heravi, A. Keivanloo, M. Rahimizadeh, M. Bakavoli, M.
Ghassemzadeh, Tetrahedron Lett., 2004, 45, 5747-5751.
17. M. Ochiai, N. Tada, Chem. Commun., 2005, 5083-5085.
18. H. Xu, Y. Zhang, J. Huang, W. Chen, Org. Lett., 2010, 12
,
3704-3707.
19. D. Xiao, L. Han, Q. Sun, Q. Chen, N. Gong, Y. Lv, F. Suzenet, G.
Guillaumet, T. Cheng, R. Li, RSC Advances, 2012, 2, 5054-
5057.
20. L. Veltri, G. Grasso, R.Rizzi, R. Mancuso, B. Gabriele, Asian J.
Org. Chem. 2016, , 560 – 567.
5
21 (a) B. Stanovnik, J. Svete, Chem. Rev. 2004, 104, 2433-2480;
(b) S. Muthusaravanan, C. Sasikumar, B. Devi Bala, S.
Perumal, Green Chem., 2014, 16, 1297-1304; (c) J. Yang, C.
Wang, X. Xie, H. Li, Y. Li, Eur. J. Org. Chem., 2010, 4189-4193.
22. (a) S. Kantevari, S. R. Patpi, B. Sridhar, P. Yogeeswari, H.
Sriram, Bioorg. Med. Chem. Lett. 2011, 21, 1214-1217; (b) S.
A. Patil, P. A. Medina, D. G. Flores, J. K. Vohs, S. Dever, L. W.
Pineda, Synthetic. Commun., 2013, 43, 2349-2352; (c) K.
Goutham, N. S. V. M. Rao Mangina, S. Suresh, P. Raghavaiah,
G. V. Karunakar, Org. Biomol. Chem., 2014, 12, 2869-2873.
23. (a) S. Ambethkar, V. Padmini, N. Bhuvanesh, J. Advanced
Research., 2015, 6, 975-985; (b) R. Sribalan, A. Lavanya, M.
Kirubavathi, V. Padmini, doi: 10.16/J.JSCS.2016.03.004. (c) S.
Ambethkar, V. Padmini, N. Bhuvanesh, New J. Chem.,
2016,40, 4705-4709 (d) I. Dhinakaran, V. Padmini, N.
Bhuvanesh. ACS Comb. Sci., 2016, 18, 236–242.
24. (a) Y. Yan, Y. Xu, B. Niu, H. Xie, Y. Liu, J. Org. Chem. 2015, 80
,
5581-5587; (b) V. K. Rao, P. Kaswan, G. M. Shelke, A. Ryan,
M. Jha, A. Kumar, Synthesis., 2015, 47, 3990-3996.
25. Crystallographic data for SA-2 and SA-6 has been deposited
with the Cambridge Crystallographic Data Centre as
supplementary publication number SA-2 CCDC 1444119 and
SA-6 CCDC 1444118
.
26. J. Safari, Z. A. Jazini, Z. Zarnegar and M. Sadeghi, Catal.Commun,
2005, 7, 763
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 7
New Journal of Chemistry
View Article Online
DOI: 10.1039/C6NJ02102F
Regioselective synthesis of benzo[4,5]imidazo[2,1-b]thiazole derivatives via amination (C-N) and intramolecular cyclization
(C-S) reaction in presence molecular iodine. This method features inexpensive catalyst, base free and metal free with simple
procedure and short reaction time.