A new route for the synthesis of functionalized benzo[d]imidazo[5,1-b]thiazol-1-amine derivatives from benzothiazole, trichloroacetamidines and terminal alkynes

Article abstract of DOI:10.1080/17415993.2020.1820010

A novel class of substituted benzo[d]imidazo[5,1-b]thiazol-1-amine derivatives was synthesized utilizing a one-pot Cu-catalyzed cycloaddition of benzothiazole, trichloroacetonitrile, various amines and terminal alkynes in acetonitrile at room temperature. The speed of this simple four-component reaction along with mild conditions, high yields, readily available starting materials, the ease of work-up without using pollutant precious metals–catalysts, and column chromatography are important features of the presented procedure.

Full text of DOI:10.1080/17415993.2020.1820010

Journal of Sulfur Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gsrp20
A new route for the synthesis of functionalized
benzo[d]imidazo[5,1-b]thiazol-1-amine derivatives
from benzothiazole, trichloroacetamidines and
terminal alkynes
Maryam Bayanati , Niloofar Parizadeh , Manijeh Nematpour , Anna
Sedaghat & Sayyed Abbas Tabatabaia
To cite this article: Maryam Bayanati , Niloofar Parizadeh , Manijeh Nematpour , Anna
Sedaghat & Sayyed Abbas Tabatabaia (2020): A new route for the synthesis of functionalized
benzo[d]imidazo[5,1-b]thiazol-1-amine derivatives from benzothiazole, trichloroacetamidines and
terminal alkynes, Journal of Sulfur Chemistry, DOI: 10.1080/17415993.2020.1820010
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JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2020.1820010
A new route for the synthesis of functionalized
benzo[d]imidazo[5,1-b]thiazol-1-amine derivatives from
benzothiazole, trichloroacetamidines and terminal alkynes
Maryam Bayanatia, Niloofar Parizadehb, Manijeh Nematpoura, Anna Sedaghatc and
Sayyed Abbas Tabatabaiaa
aDepartment of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical
Sciences, Tehran, Iran; bFaculty of Chemistry, Institute of Organic Chemistry, University of Vienna, Vienna,
Austria; cStudent Research Committee, (Department and Faculty of pharmacy), Shahid Beheshti University of
Medical Sciences, Tehran, Iran
ABSTRACT
ARTICLE HISTORY
Received 4 July 2020
Accepted 29 August 2020
A novel class of substituted benzo[d]imidazo[5,1-b]thiazol-1-amine
derivatives was synthesized utilizing a one-pot Cu-catalyzed cycload-
dition of benzothiazole, trichloroacetonitrile, various amines and
terminal alkynes in acetonitrile at room temperature. The speed of
this simple four-component reaction along with mild conditions,
high yields, readily available starting materials, the ease of work-
up without using pollutant precious metals–catalysts, and column
chromatography are important features of the presented procedure.
KEYWORDS
Benzo[d]imidazo[5,1-
b]thiazol-1-amine; C-H
Activation; Cu-catalyzed;
One-pot
1. Introduction
These Sulfur-containing heterocycles commonly exist and are isolated from natural prod-
ucts, and their various biological and pharmaceutical applications have attracted much
attention [1–4]. Benzo-thiazolo-imidazole is a fuzed tricyclic sulfur-containing heterocy-
cle and valuable building block with biological activity ranging from antineoplastic [5,6],
antibacterial [7–10], to labeled molecules as an excellent fluoroprobe for PET scan analysis
of Alzheimer disease (see Figure 1) [11–13].
CONTACT Sayyed Abbas Tabatabaia
sa_tabatabai@sbmu.ac.ir
Supplemental data for this article can be accessed here. https://doi.org/10.1080/17415993.2020.1820010
© 2020 Informa UK Limited, trading as Taylor & Francis Group

2
M. BAYANATI ET AL.
Figure 1. YM-201627 (anti-cancer) and CIBT (PET tracer) with benzothiazolo-imidazole core.
Scheme 1. Synthesis of various benzo-thiazolo-imidazole derivatives.
The less and costly available materials, low yields, complicated workup, and toxic cata-
lysts still limits the synthesis of this scaffold [14–17]. Therefore, an efficient simple method
to synthesize this scaffold is still ongoing [18–22]. Cu-catalyzed C-H activation is a remark-
able method for preparing heterocyclic compounds [23,24]. Various multi-component
reactions (MCRs) using copper- a catalyst for creating new heterocyclic compounds have
been previously reported by our research group [25–29].
Continuing our previous work and given the importance of substituted benzo[d]
imidazo[5,1-b]thiazol-1-amine derivatives, we developed a highly efficient method
copper-catalyzed synthesis, one-pot four-component reaction of benzothiazole 1, termi-
nal alkynes 2, trichloroacetonitrile 3 and various amines 4. In practice, the experiments
were carried out using in situ preparation of trichloroacetamidines intermediate 5 from
the reaction of
trichloroacetonitrile 3 and various amines 4. The electron-withdrawing effect of the -
CCl3 makes the nitrile group of trichloroacetonitrile prone to the attack of nucleophilic
amine (see Scheme 1).
2. Results and discussion
The reaction conditions optimization were done using phenylacetylene (1.0 mmol), ben-
zothiazole (1.5 mmol), trichloroacetonitrile (1.0 mmol) and benzylamine (1.5 mmol) as a
model of precursors. Copper and a few of its salts and various solvents were investigated
to optimize the reaction. The best results were obtained using 10 mol % of cuprous iodide
(CuI) as catalyst and acetonitrile (MeCN) as solvent respectively. This optimal catalytic

JOURNAL OF SULFUR CHEMISTRY
3
Table 1. Optimization of reaction conditions for the formation of
product 6a from 1.5 mmol of benzylamine, 1.5 mmol of benzoth-
iazole, 1.0 mmol of phenylacetylene, 1.0 mmol of trichloroacetoni-
trile, 10 mol % of copper salt as the catalyst and 1.0 mmol of the TEA
at room temperature.
Entry
Catalyst
Solvent
Yield (%)a
1b
2
3
4
5
6
7
8
9
CuI
CuI
CuI
MeCN
DMSO
DMF
88
32
22
70
70
30
54
42
16
16
-
CuI
THF
CuCl
CuCl
CuBr
CuBr
CuBr
Cu(OAc)2
Cu
MeCN
Toluene
MeCN
THF
DMF
MeCN
THF
10
11
12
Cu
MeCN
-
a Reaction time 2 h.
b5 mol% catalyst, reaction time was 5 h.
Table 2. Synthesis of various benzo[d]imidazo[5,1-b]thiazol-1-
amine derivatives.
Compound
R
R’
Yield (%)
6a
6b
6c
6d
6e
6f
6g
6h
6i
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Pr
Ph-CH2
4-Me-C6H4-CH2
4-OMe-C6H4-CH2
4-F-C6H4-CH2
Ph
4-Me-C6H4
4-OMe-C6H4
4-F-C6H4
4-F-C6H4-CH2
4-Me-C6H4-CH2
4-F-C6H4-CH2
4-Me-C6H4-CH2
88
85
79
90
81
80
78
82
76
77
80
83
6j
K
l
Pr
Bu
Bu
effect of CuI is probably due to its more solubility in the solvent. The experiments have
shown that the use of 1.0 mmol of triethylamine as a base significantly accelerates the
reaction rate. The optimization results are summarized in Table 1.
Finally, twelve analogs of benzo[d]imidazo[5,1-b]thiazol-1-amine derivatives were syn-
thesized from benzothiazole, trichloroacetonitrile, terminal alkynes and amines with a
diversity of substituents (electron-withdrawing or electron-donating) on the aromatic
rings (see Table 2).

4
M. BAYANATI ET AL.
Scheme 2. Plausible formation mechanism of compounds 6.
1
The structural spectra of final product 6a-6l were assigned using Infrared, H NMR,
13C NMR, and mass spectroscopy. As an example, the 1H NMR spectrum of compound
6a, displayed a singlet signal for the NH group (δ = 5.21 ppm) and two singlet peaks for
H
methylene groups (δ = 3.04 and 3.55 ppm). Also, characteristic multiplet signals for the
H
phenyl protons were seen in the aromatic zone. The 13C NMR spectrum of 6a displayed
16 signals in accordance with the desired structure. The mass spectrum of compound 6a
showed a signal of molecular ion at m/z = 369. The NMR spectra of compounds 6b-l were
similar to those of 6a and exhibited corresponding signals due to structural differences.
A plausible mechanism for the formation of compounds 6 is shown in Scheme 2.
Initially, the nucleophilic addition of amine 4 to trichloroacetonitrile 3 leads to the for-
mation of trichloromethylamidine adduct 5 which is susceptible to a substitution by
negatively charged nitrogen of benzothiazole to leave CCl3 group. In practice, negatively
charged nitrogen can be produced by the attack of in situ prepared corresponding cop-
per acetylide intermediate (CuC ≡CR) to number 2 carbon of the benzothiazole ring. The
six-membered complex A resulting from the coordination of copper with a triple bond
of substituted acetylene and NH group facilitates the ring formation. Finally, product 6 is
formed upon the tautomerization of the intermediates C to create an aromatic imidazole
ring. The absence of halogen to facilitate ring formation makes our method distinct from
the hybrid of alkyne hydroamination / Heck reaction. The uptake of protons in the reaction
medium by TEA probably contributes to the improvement of the reaction.
3. Conclusion
In conclusion, we have developed a simple CuI-catalyzed one-pot four-component reac-
tion involving trichloroacetonitrile, benzothiazole, terminal acetylene, and various amines.

JOURNAL OF SULFUR CHEMISTRY
5
This novel method involves the formation of three new C–N bonds in an intermolecular
cycloaddition reaction for efficient synthesizing benzo[d]imidazo[5,1-b]thiazol-1-amine
derivatives. The present work introduces an excellent alternative over earlier methods
in terms of high yields, operational simplicity, availability of raw materials, and mild
conditions.
4. Experimental
All chemicals were used without further purification and provided from Merck com-
pany. Melting points (m.p), IR spectra, and CHN Elemental analyses were carried out
using an Electrothermal 9100 apparatus, Shimadzu IR-460 spectrometer, and Heraeus
CHN-O-Rapid analyzer, respectively. The melting points are uncorrected. Finnigan-MAT-
8430EI-MS, was adjusted to achieve mass spectrometer; at 70 eV; in m/z (rel. %). 1H and
13C NMR spectra were recorded by Bruker DRX-500 Avance instrument, TMS as internal
standard, and CDCl3 as tested solvent at 500.1 and 125.7 MHz, respectivley. The abbrevi-
ations applied for NMR signals: s = singlet, d = doublet, t = triplet, m = multiplet, and
δ in ppm, J in Hz.
4.1. General procedure for preparation of compounds 6
Trichloroacetonitrile 3 (1.0 mmol) and appropriate amine 4 (1.5 mmol) were reacted
exothermically under a neat condition for 15 min at 25°C. Then, benzothiazole 1 (1.5
mmol), substituted acetylene 2 (1.0 mmol), CuI (0.1 mmol), and TEA (1.0 mmol) were
mixed in acetonitrile (3 ml). Then after, it was added slowly to the primary reaction, and
stirring is continued for 2 h. The reaction progress is monitored using thin-layer chro-
matography (ethyl acetate/hexane 1:3). The mixture was diluted with 2.0 mL of CHCl3 and
then was shaken well twice with 2.0 mL saturated aqueous solution of NH4Cl to remove
CuI. The organic fraction was dried over anhydrous sodium sulfate, and then filtered off,
and the solvent was evaporated under reduced pressure, and crude solid was washed with
normal hexane to afford the pure product.
N, 3-Dibenzylbenzo[d]imidazo[5,1-b]thiazol-1-amine (6a): White powder; yield: 0.32 g
(88%); mp: 144–147°C. IR (KBr) (νmax, cm−1): 3312, 1640, 1601, 1161. 1H-NMR
(500 MHz, CDCl3): δ = 3.04 (s, 2 H, CH2), 3.55 (s, 2 H, CH2), 5.21 (s, 1 H, NH), 7.19
H
(d, 3J = 7.6, 2 H, Ar), 7.23 (t, 3J = 7.7, 1 H, Ar), 7.27–7.33 (m, 7 H, Ar), 7.45 (d, 3J = 7.7,
2 H, Ar), 7.47 (d, 3J = 7.9, 1 H, Ar), 7.88 (d, 3J = 7.9, 1 H, Ar). 13C-NMR (125.7 MHz,
CDCl3): δ = 33.0 (CH2), 42.3 (CH2), 126.1 (2CH), 126.7 (2 CH), 127.4 (2 CH), 127.7
C
(CH), 128.7 (2CH), 129.2 (C), 130.0 (2CH), 132.5 (2CH), 132.9 (2CH), 133.0 (CH), 142.1
(C), 147.3 (C), 153.4 (C), 164.4 (C). MS: m/z (%) =369 (M+, 4), 292 (21), 278 (39), 263
(11), 106 (73), 91 (55), 77 (100). Anal. Calc. for C23H19N3S (369.48): C, 74.77; H, 5.18; N,
11.37%. Found: C, 74.72; H, 5.15; N, 11.39%.
Benzyl-N-(4-methylbenzyl)benzo[d]imidazo[5,1-b]thiazol-1-amine (6b): White
powder; yield: 0.34 g (85%); mp: 135–137°C. IR (KBr) (νmax, cm−1): 3318, 1641, 1600,
1151. 1H-NMR (500 MHz, CDCl3): δ = 2.09 (s, 3 H, Me), 3.02 (s, 2 H, CH2), 3.66 (s, 2
H
H, CH2), 5.00 (s, 1 H, NH), 7.17 (d, 3J = 7.7, 2 H, Ar), 7.24 (t, 3J = 7.7, 2 H, Ar), 7.28–7.31
(m, 3 H, Ar), 7.43 (t, 3J = 7.8, 1 H, Ar), 7.58 (d, 3J = 7.8, 2 H, Ar), 7.60 (t, 3J = 7.9, 1 H,

6
M. BAYANATI ET AL.
Ar), 7.87 (d, 3J = 7.9, 1 H, Ar), 8.01 (d, 3J = 7.9, 1 H, Ar). 13C-NMR (125.7 MHz, CDCl3):
δ = 24.1 (Me), 34.4CH2), 41.2 (CH2), 126.2 (2 CH), 126.6 (C), 127.3 (2 CH), 127.8 (CH),
C
128.7 (2 CH), 130.0 (CH), 130.7 (2 CH), 131.7 (2 CH), 132.5 (CH), 135.7 (C), 136.6 (C),
144.7 (C), 152.4 (C), 153.4 (C), 163.2 (C), 165.7 (C). MS: m/z (%) = 383 (M+, 2), 306 (22),
292 (29), 334 (37), 263 (100), 120 (33), 91 (50), 77 (40). Anal. Calc. for C24H21N3S (383.51):
C, 75.16; H, 5.52; N, 10.96%. Found: C, 75.12; H, 5.50; N, 10.94%.
Benzyl-N-(4-methoxybenzyl)benzo[d]imidazo[5,1-b]thiazol-1-aminee (6c): Cream
powder; yield: 0.37 g (79%); mp: 148–150°C. IR (KBr) (νmax, cm−1): 3300, 1643, 1600,
1198. 1H-NMR (500 MHz, CDCl3): δ = 2.46 (s, 2 H, CH2), 3.07 (s, 2 H, CH2), 4.12 (s, 3
H
H, OMe), 5.11 (s, 1 H, NH), 7.10 (d, 3J = 7.7, 2 H, Ar), 7.27 (t, 3J = 7.7, 1 H, Ar), 7.28–7.35
(m, 6 H, Ar), 7.38 (d, 3J = 7.7, 2 H, Ar), 7.50 (d, 3J = 7.9, 1 H, Ar), 7.88 (d, 3J = 7.9, 1 H,
Ar). 13C-NMR (125.7 MHz, CDCl3): δ = 33.2 (CH2), 47.8 (CH2), 57.4 (OMe), 126.8 (2
C
CH), 127.5 (C), 128.7 (2 CH), 129.8 (CH), 130.0 (2 CH), 132.8 (2 CH), 132.9 (2 CH), 132.5
(2 CH), 136.7 (C), 141.1 (C), 147.9 (C), 153.1 (C), 154.8 (C), 164.2 (C), 166.8 (C).MS: m/z
(%) = 399 (M+, 2), 322 (21), 292 (38), 278 (35), 121 (33), 107 (36), 91 (100), 77 (61). Anal.
Calc. for C24H21N3OS (399.51): C, 72.15; H, 5.30; N, 10.52%. Found: C, 72.12; H, 5.34; N,
10.57%.
Benzyl-N-(4-fluorobenzyl)benzo[d]imidazo[5,1-b]thiazol-1-amine (6d):
Cream
powder; yield: 0.34 g (90%); mp: 182–185°C. IR (KBr) (νmax, cm−1): 3167, 1621, 1600,
1155. 1H-NMR (500 MHz, CDCl3): δ = 3.02 (s, 2 H, CH2), 3.65 (s, 2 H, CH2), 5.24 (s,
H
1 H, NH), 7.20 (d, 3J = 7.7, 2 H, Ar), 7.25 (t, 3J = 7.7, 2 H, Ar), 7.25–7.30 (m, 7 H, Ar),
3
3
7.47 (d, J = 7.9, 1 H, Ar), 8.13 (d, J = 7.9, 1 H, Ar). 13C-NMR (125.7 MHz, CDCl3):
δ = 32.8(CH2), 41.8 (CH2), 126.1 (2 CH), 128.7 (CH), 129.2 (2 CH), 130.0 (CH), 131.6
C
(CH), 131.9 (C), 132.5 (2 CH), 132.9 (2 CH), 133.0 (C), 134.1 (CH), 135.7 (CH), 140.1
(C), 141.2 (C), 152.5 (C), 154.2 (C), 162.2 (C), 165.6 (C).MS: m/z (%) = 387 (M+, 2), 310
(44), 296 (22), 292 (29), 95 (100), 91 (51), 77 (42). Anal. Calc. for C23H18FN3S (387.47):
C, 71.29; H, 4.68; N, 10.84%. Found: C, 71.25; H, 4.62; N, 10.89%.
Benzyl-N-phenylbenzo[d]imidazo[5,1-b]thiazol-1-amine (6e): White powder; yield:
0.31 g (81%); mp: 172–175°C. IR (KBr) (νmax, cm−1): 3189, 1643, 1591, 1160. 1H-NMR
3
(500 MHz, CDCl3): δ = 3.11 (s, 2 H, CH2), 5.89 (s, 1 H, NH), 7.17 (d, J = 7.6, 2 H,
H
Ar), 7.24 (t, 3J = 7.7, 1 H, Ar), 7.31–7.36 (m, 5 H, Ar), 7.49 (d, 3J = 7.7, 2 H, Ar), 7.59
(d, 3J = 7.9, 1 H, Ar), 7.78 (d, 3J = 7.9, 1 H, Ar), 8.00 (d, 3J = 7.7, 2 H, Ar). 13C-NMR
(125.7 MHz, CDCl3): δ = 34.7 (CH2), 126.9 (2 CH), 127.4 (2 CH), 127.8 (CH), 128.8 (2
C
CH), 130.0 (C), 130.2 (CH), 130.8 (2 CH), 131.7 (2 CH), 132.9 (2 CH), 135.8 (C), 144.7
(C), 147.3 (C), 152.9 (C), 154.5 (C), 165.9 (C). MS: m/z (%) = 355 (M+, 9), 278 (44), 264
(10), 263 (21), 91 (100), 77 (65). Anal. Calc. for C22H17N3S (355.46): C, 74.34; H, 4.82; N,
11.82%. Found: C, 74.42; H, 4.84; N, 11.87%.
Benzyl-N-(p-tolyl)benzo[d]imidazo[5,1-b]thiazol-1-amine (6f): Cream powder;
1
yield: 0.33 g (80%); mp: 162–165°C. IR (KBr) (νmax, cm−1):3219, 1623, 1590, 1135. H-
NMR (500 MHz, CDCl3): δ = 2.22 (s, 3 H, Me), 2.56 (s, 2 H, CH2), 5.87 (s, 1 H, NH),
H
7.30–7.35 (m, 7 H, Ar), 7.47–7.51 (m, 4 H, Ar), 7.59 (t, 3J = 7.7, 1 H, Ar), 7.98 (d, 3J = 7.9,
1 H, Ar). 13C-NMR (125.7 MHz, CDCl3): δ = 30.0 (Me), 35.0 (CH2), 128.8 (2 CH), 129.2
C
(2 CH), 129.3 (C), 129.4 (2 CH), 130.3 (2 CH), 130.8 (CH), 131.8 (2 CH), 132.5 (CH), 134.3
(CH), 134.4 (CH), 134.9 (C), 135.0 (C), 144.7 (C), 153.4 (C), 164.5 (C), 167.9 (C). MS: m/z

JOURNAL OF SULFUR CHEMISTRY
7
(%) = 369 (M+, 8), 292 (33), 278 (10), 106 (21), 91 (50), 77 (68). Anal. Calc. for C23H19N3S
(369.48): C, 74.77; H, 5.18; N, 11.37%. Found: C, 74.72; H, 5.14; N, 11.34%.
Benzyl-N-(4-methoxyphenyl)benzo[d]imidazo[5,1-b]thiazol-1-amine(6g):
White
powder; yield: 0.35 g (78%); mp: 165–167°C. IR (KBr) (νmax, cm−1): 3299, 1641, 1590,
1129. 1H-NMR (500 MHz, CDCl3): δ = 2.93 (s, 2 H, CH2), 4.13 (s, 3 H, OMe), 5.99 (s, 1
H
H, NH), 7.19 (d, 3J = 7.7, 2 H, Ar), 7.22 (t, 3J = 7.7, 1 H, Ar), 7.24–7.32 (m, 6 H, Ar), 7.38
(d, 3J = 7.7, 2 H, Ar), 7.47 (d, 3J = 7.9, 1 H, Ar), 7.88 (d, 3J = 7.9, 1 H, Ar). 13C-NMR
(125.7 MHz, CDCl3): δ = 33.0 (CH2), 56.6 (OMe), 126.1 (2 CH), 126.7 (2 CH), 127.4 (2
C
CH), 127.8 (CH), 128.7 (2 CH), 129.2 (CH), 129.5 (C), 130.0 (2 CH), 130.6 (2 CH), 132.5
(C), 142.1 (C), 147.3 (C), 150.2 (C), 160.1 (C), 164.3 (C). MS: m/z (%) = 385 (M+, 8), 308
(22), 278 (55), 263 (20), 122 (33), 107 (100), 91 (50), 77 (66). Anal. Calc. for C23H19N3OS
(385.48): C, 71.66; H, 4.97; N, 10.90%. Found: C, 71.62; H, 4.94; N, 10.91%.
Benzyl-N-(4-fluorophenyl)benzo[d]imidazo[5,1-b]thiazol-1-amine (6h): Cream
powder; yield: 0.31 g (82%); mp: 181–184°C. IR (KBr) (νmax, cm−1): 3189, 1629, 1600,
1134. 1H-NMR (500 MHz, CDCl3): δ = 2.01 (s, 2 H, CH2), 6.00 (s, 1 H, NH), 7.18 (d,
H
3J = 7.6, 2 H, Ar), 7.23 (t, 3J = 7.7, 1 H, Ar), 7.24–7.31 (m, 4 H, Ar), 7.43 (d, 3J = 7.7, 2
H, Ar), 7.58 (t, 3J = 7.9, 2 H, Ar), 7.60 (d, 3J = 7.9, 1 H, Ar), 8.00 (d, 3J = 7.7, 1 H, Ar).
13C-NMR (125.7 MHz, CDCl3): δ = 32.9 (CH2), 127.3 (2 CH), 127.8 (2 CH), 128.7 (2
C
CH), 128.9 (C), 129.2 (2 CH), 130.0 (2 CH), 130.1 (2 CH), 132.9 (CH), 135.7 (C), 136.8
(C), 144.7 (C), 147.3 (C), 154.2 (C), 159.5 (C), 165.9 (C).MS: m/z (%) = 373 (M+, 10), 296
(15), 282 (18), 278 (74), 95 (100), 91 (50), 77 (61). Anal. Calc. for C22H16FN3S (373.45):
C, 70.76; H, 4.32; N, 11.25%. Found: C, 70.73; H, 4.30; N, 11.27%.
Butyl-N-(4-fluorobenzyl)benzo[d]imidazo[5,1-b]thiazol-1-amine (6i): White powder;
1
yield: 0.29 g (76%); mp: 122–125°C. IR (KBr) (νmax, cm−1):3212, 1699, 1593, 1188. H-
NMR (500 MHz, CDCl3): δ = 0.88 (3 H, t, 3J = 6.7 Hz, Me), 1.38–1.40 (2 H, m, CH2),
H
1.46–1.49 (2 H, m, CH2), 2.14 (2 H, t, 3J = 6.7 Hz, CH2), 3.10 (s, 2 H, CH2), 5.09 (s, 1 H,
NH), 7.19 (d, 3J = 7.8, 2 H, Ar), 7.25 (t, 3J = 7.9, 1 H, Ar), 7.33 (t, 3J = 7.9, 1 H, Ar), 7.60
(d, 3J = 7.9, 1 H, Ar), 7.72 (d, 3J = 7.9, 1 H, Ar), 8.01 (d, 3J = 7.8, 2 H, Ar). 13C-NMR
(125.7 MHz, CDCl3): δ = 14.0 (Me), 18.4 (CH2), 20.9 (CH2), 22.2 (CH2), 40.0 (CH2),
C
126.1 (2 CH), 127.3 (2 CH), 127.7 (CH), 128.9 (C), 129.9 (CH), 130.1 (CH), 131.8 (CH),
135.7 (C), 144.8 (C), 152.7 (C), 153.8 (C), 162.2 (C), 165.0 (C). MS: m/z (%) = 353 (M+,
2), 296 (20), 258 (19), 244 (61), 110 (100), 95 (51), 57 (97). Anal. Calc. for C20H20FN3S
(353.46): C, 67.96; H, 5.70; N, 11.89%. Found: C, 67.91; H, 5.73; N, 11.83%.
Butyl-N-(4-methylbenzyl)benzo[d]imidazo[5,1-b]thiazol-1-amine
(6j):
Cream
powder; yield: 0.29 g (77%); mp: 112–115°C. IR (KBr) (νmax, cm−1): 3111, 1649, 1591,
1121. 1H-NMR (500 MHz, CDCl3): δ = 0.87 (3 H, t, 3J = 6.7 Hz, Me), 1.37–1.40 (2 H,
H
m, CH2), 1.45–1.47 (2 H, m, CH2), 1.90 (2 H, t, 3J = 6.7 Hz, CH2), 2.44 (s, 3 H, Me), 2.92 (s,
2 H, CH2), 5.11 (s, 1 H, NH), 7.16–7.18 (m, 2 H, Ar), 7.23 (t, 3J = 7.6, 1 H, Ar), 7.31–7.35
(m, 3 H, Ar), 7.38 (d, 3J = 7.9, 1 H, Ar), 7.86 (d, 3J = 7.9, 1 H, Ar). 13C-NMR (125.7 MHz,
CDCl3): δ = 13.9 (Me), 18.5 (CH2), 21.8 (CH2), 22.2 (CH2), 33.1 (Me), 39.5 (CH2), 126.1
C
(2 CH), 126.8 (C), 127.4 (2 CH), 127.8 (CH), 129.5 (C), 130.0 (CH), 130.7 (2 CH), 147.4
(C), 151.9 (C), 155.9 (C), 162.1 (C), 164.1 (C). MS: m/z (%) = 349 (M+, 9), 292 (17), 258

8
M. BAYANATI ET AL.
(45), 244 (20), 91 (100), 57 (61). Anal. Calc. for C21H23N3S (349.49): C, 72.17; H, 6.63; N,
12.02%. Found: C, 72.19; H, 6.60; N, 12.06%.
N-(4-Fluorobenzyl)-3-pentylbenzo[d]imidazo[5,1-b]thiazol-1-amine(6k): Cream pow-
der; yield: 0.29 g (80%); mp: 127–130°C. IR (KBr) (νmax, cm−1): 3212, 1622, 1600, 1154.
3
1H-NMR (500 MHz, CDCl3): δ = 0.91 (3 H, t, J = 6.7 Hz, Me), 1.19–1.22 (2 H, m,
H
CH2), 1.24–1.31 (4 H, m, CH2), 2.01 (2 H, t, 3J = 6.7 Hz, CH2), 2.99 (s, 2 H, CH2), 6.01
3
3
3
(s, 1 H, NH), 7.41 (d, J = 7.9, 2 H, Ar), 7.58 (t, J = 7.8, 1 H, Ar), 7.70 (t, J = 7.8, 1
H, Ar), 7.72 (d, 3J = 7.8, 1 H, Ar),7.85 (d, 3J = 7.8, 1 H, Ar), 7.99 (d, 3J = 7.9, 2 H, Ar).
13C-NMR (125.7 MHz, CDCl3): δ = 13.7 (Me), 20.7 (CH2), 21.9 (CH2), 22.0 (CH2), 22.2
C
(CH2), 38.0 (CH2), 127.3 (2 CH), 129.8 (CH), 130.1 (2 CH), 131.2 (CH), 131.5 (CH), 132.0
(C), 133.0 (C), 135.6 (CH), 144.7 (C), 152.2 (C), 154.8 (C), 160.2 (C), 163.8 (C). MS: m/z
(%) = 367 (M+, 9), 296 (17), 272 (45), 258 (20), 106 (25), 95 (100), 71 (61). Anal. Calc. for
C21H22FN3S (367.48): C, 68.64; H, 6.03; N, 11.43%. Found: C, 68.61; H, 6.00; N, 11.47%.
N-(4-Methylbenzyl)-3-pentylbenzo[d]imidazo[5,1-b]thiazol-1-amine(6l): Cream pow-
der; yield: 0.30 g (83%); mp: 119–121°C. IR (KBr) (νmax, cm−1): 3262, 1641, 1567, 1124.
3
1H-NMR (500 MHz, CDCl3): δ = 0.97 (3 H, t, J = 6.7 Hz, Me), 1.24–1.27 (4 H, m,
H
CH2), 1.53–1.56 (2 H, m, CH2), 2.13 (2 H, t, 3J = 6.7 Hz, CH2), 2.15 (s, 3 H, Me), 2.47
(s, 2 H, CH2), 4.90 (s, 1 H, NH), 7.16–7.23 (m, 3 H, Ar), 7.30–7.36 (m, 3 H, Ar), 7.40 (d,
3J = 7.9, 1 H, Ar), 7.90 (d, 3J = 7.8, 1 H, Ar). 13C-NMR (125.7 MHz, CDCl3): δ = 13.8
C
(Me), 20.8 (CH2), 22.2 (CH2), 22.3 (CH2), 30.7 (CH2), 33.0 (Me), 126.2 (2 CH), 127.4 (2
CH), 130.2 (CH), 130.5 (CH), 130.7 (CH), 130.9 (C), 132.0 (CH), 142.1 (C), 146.8 (C),
146.9 (C), 149.7 (C), 149.8 (C), 160.7 (C), 164.3 (C).MS: m/z (%) = 363 (M+, 9), 292 (17),
272 (45), 258 (20), 120 (25), 91 (100), 71 (61). Anal. Calc. for C22H25N3S (363.52): C, 72.69;
H, 6.93; N, 11.56%. Found: C, 72.63; H, 6.90; N, 11.52%.
Acknowledgements
This work was supported by the National Institute for Medical Research Development (NIMAD,
project No. 962440).
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by National Institute for Medical Research Development [grant number
962440].
References
[1] Dauban P, Dodd RH. Synthesis of cyclic sulfonamides via intramolecular copper-catalyzed
reaction of unsaturated iminoiodinanes. Org Lett. 2000;2:2327–2329.
[2] Katritzky AR, Wu J, Rachwal S, et al. Preparation of 6-, 7- and 8-membered sultams
by friedel-crafts cyclization of ω-phenylalkanesulfamoyl chlorides. Org Prep Proced Int.
1992;24:463–467.
[3] Greig IR, Tozer MJ, Wright PT. Synthesis of cyclic sulfonamides through intramolecular diels-
alder reactions. Org Lett. 2001;3:369–371.

JOURNAL OF SULFUR CHEMISTRY
9
[4] Gan Z, Yan Q, Li G, et al. Copper-catalyzed domino synthesis of sulfur-containing heterocycles
using carbon disulfide as a building block. Adv Synth Catal. 2019;361:4558–4567.
[5] Amino N, Ideyama Y, Yamano M, et al. YM-201627: AN orally active antitumor agent with
selective inhibition of vascular endothelial cell proliferation. Cancer Lett. 2006;238:119–127.
[6] Kamal A, Sultana F, Ramaiah MJ, et al. 3-Substituted 2-Phenylimidazo[2,1-b]benzothiazoles:
synthesis, anticancer activity, and inhibition of tubulin polymerization. ChemMedChem.
2012;7:292–300.
[7] Venkatesan AM, Gu Y, Santos OD, et al. Structure-activity relationship of 6-methylidene
penems bearing tricyclic heterocycles as broad-spectrum β-lactamase inhibitors: crystallo-
graphic structures show unexpected binding of 1,4-thiazepine intermediates. J Med Chem.
2004;47:6556–6568.
[8] Farag AM, Mayhoub AS, Barakat SE, et al. Synthesis of new N-phenylpyrazole derivatives with
potent antimicrobial activity. Bioorganic Med Chem. 2008;16:4569–4578.
[9] Al-Tel TH, Al-Qawasmeh RA, Zaarour R. Design, synthesis and in vitro antimicrobial evalua-
tion of novel imidazo[1,2-a]pyridine and imidazo[2,1-b][1,3]benzothiazole motifs. Eur J Med
Chem. 2011;46:1874–1881.
[10] Palkar M, Noolvi M, Sankangoud R, et al. Synthesis and antibacterial activity of a novel series
of 2,3-diaryl-substituted-imidazo(2,1-b)-benzothiazole derivatives. Arch Pharm (Weinheim).
2010;343:353–359.
[11] Yousefi BH, Manook A, Drzezga A, et al. Synthesis and evaluation of 11C-labeled imidazo
[2,1-b] benzothiazoles (IBTs) as PET tracers for imaging β-amyloid plaques in Alzheimer’s
disease. J Med Chem. 2011;54:949–956.
[12] Alagille D, Dacosta H, Baldwin RM, et al. 2-Arylimidazo[2,1-b]benzothiazoles: a new family
of amyloid binding agents with potential for PET and SPECT imaging of Alzheimer’s brain.
Bioorganic Med Chem Lett. 2011;21:2966–2968.
[13] Yousefi BH, Drzezga A, von Reutern B, et al. A novel 18F-labeled imidazo[2,1- b ]benzoth-
iazole (IBT) for high-contrast PET imaging of β-amyloid plaques. ACS Med Chem Lett.
2011;2:673–677.
[14] Balwe SG, Jeong YT. Iron-catalyzed unprecedented formation of benzo[d]imidazo
[2,1-b]thiazoles under solvent-free conditions. RSC Adv. 2016;6:107225–107232.
[15] Balwe SG, Lim KT, Cho BG, et al. A pot-economical and green synthesis of novel
(benzo[d]imidazo[2,1-b]thiazol-3-yl)-2H-chromen-2-one in ethanol–PEG-600 under
catalyst-free conditions. Tetrahedron. 2017;73:3564–3570.
[16] Wang J, Li J, Zhu Q. Copper-promoted cycloaddition of α-methylenyl isocyanides with
benzothiazoles: tunable access to benzo[d]imidazothiazoles. Org Lett. 2015;17:5336–5339.
[17] Wu Z, Huang Q, Zhou X, et al. Synthesis of pyrido[1,2-a]benzimidazoles through a copper-
catalyzed cascade C-N coupling process. European J Org Chem. 2011;2011:5242–5245.
[18] Mishra S, Monir K, Mitra S, et al. Fecl /ZnI -catalyzed synthesis of benzo[ d ]imidazo
2
[2,1- b ]thiazole through aerobic oxidat3ive cyclization between 2-aminobenzothiazole and
Ketone. Org Lett. 2014;16:6084–6087.
[19] Kumar GS, Ragini SP, Kumar AS, et al. A copper-catalyzed multi-component reaction accessing
fused imidazo-heterocycles via C-H functionalization. RSC Adv. 2015;5:51576–51580.
[20] Rassokhina IV, Tikhonova TA, Kobylskoy SG, et al. Synthesis of imidazo[2,1-b]thiazoles via
copper-catalyzed A3-coupling in batch and continuous flow. J Org Chem. 2017;82:9682–9692.
[21] Xie Y, Chen X, Wang Z, et al. Metal-free oxidative cyclization of 2-aminobenzothiazoles and
cyclic ketones enabled by the combination of elemental sulfur and oxygen. Green Chem.
2017;19:4294–4298.
[22] Vidyacharan S, Shinde AH, Satpathi B, et al. A facile protocol for the synthesis of
3-aminoimidazo-fused heterocycles via the Groebke-Blackburn-Bienayme reaction under
catalyst-free and solvent-free conditions. Green Chem. 2014;16:1168–1175.
[23] Yavari I, Nematpour M, Hossaini Z. Ph3P-mediated one-pot synthesis of functionalized
3,4-dihydro-2H-1,3-thiazines from N,N1-dialkylthioureas and activated acetylenes in water.
Monatsh Chem. 2010;141:229–232.

10
M. BAYANATI ET AL.
[24] Yang D, An B, Wei W, et al. Copper-catalyzed domino synthesis of nitrogen heterocycle-
fused benzoimidazole and 1,2,4-benzothiadiazine 1,1-dioxide derivatives. ACS Comb Sci.
2015;17:113–119.
[25] Dastjerdi HF, Nematpour M, Rezaee E, et al. One-pot synthesis of highly functionalized benzo
[1,3] thiazine from isocyanides, aniline, and heterocumulene via Cu-catalyzed intramolecular
C-H activation reactions. J Chinese Chem Soc. 2019;66:1537–1541.
[26] Nematpour M, Rezaee E, Tabatabai SA, et al. A copper-catalyzed synthesis of functional-
ized quinazolines from isocyanides and aniline tri- and dichloroacetonitrile adducts through
intramolecular C-H activation. Synlett. 2017;28:1441–1444.
[27] Nematpour M, Rezaee E, Jahani M, et al. Synthesis of functionalized benzothiadiazine 1,1-
dioxide derivatives via intramolecular C–H activation reactions of trichloroacetamidine and
benzenesulfonyl chloride. Tetrahedron Lett. 2018;59:2054–2056.
[28] Nematpour M, Rezaee E, Jahani M, et al. Ultrasound-assisted synthesis of highly functionalized
benzo[1,3]thiazine via Cu-catalyzed intramolecular C–H activation reaction from isocyanides,
aniline-benzoyl(acetyl) isothiocyanate adduct. Ultrason Sonochem. 2019;50:1–5.
[29] Nematpour M, Sedaghat A, Dastjerdi HF, et al. Tandem synthesis of highly functionalized
1,2,3-benzotriazines from isocyanides, aniline and dialkyl azadicarboxylate via Cu-catalyzed
intramolecular C-H activation reactions. Tetrahedron Lett. 2020;61:151649.